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Adenosine Receptors and Neurological Disease: Neuroprotection and Neurodegeneration

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Book cover Adenosine Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 193))

Abstract

Adenosine receptors modulate neuronal and synaptic function in a range of ways that may make them relevant to the occurrence, development and treatment of brain ischemic damage and degenerative disorders. A1 adenosine receptors tend to suppress neural activity by a predominantly presynaptic action, while A2A adenosine receptors are more likely to promote transmitter release and postsynaptic depolarization. A variety of interactions have also been described in which adenosine A1 or A2 adenosine receptors can modify cellular responses to conventional neurotransmitters or receptor agonists such as glutamate, NMDA, nitric oxide and P2 purine receptors. Part of the role of adenosine receptors seems to be in the regulation of inflammatory processes that often occur in the aftermath of a major insult or disease process. All of the adenosine receptors can modulate the release of cytokines such as interleukins and tumor necrosis factor-α from immune-competent leukocytes and glia. When examined directly as modifiers of brain damage, A1 adenosine receptor (AR) agonists, A2AAR agonists and antagonists, as well as A3AR antagonists, can protect against a range of insults, both in vitro and in vivo. Intriguingly, acute and chronic treatments with these ligands can often produce diametrically opposite effects on damage outcome, probably resulting from adaptational changes in receptor number or properties. In some cases molecular approaches have identified the involvement of ERK and GSK-3β pathways in the protection from damage. Much evidence argues for a role of adenosine receptors in neurological disease. Receptor densities are altered in patients with Alzheimer’s disease, while many studies have demonstrated effects of adenosine and its antagonists on synaptic plasticity in vitro, or on learning adequacy in vivo. The combined effects of adenosine on neuronal viability and inflammatory processes have also led to considerations of their roles in Lesch–Nyhan syndrome, Creutzfeldt–Jakob disease, Huntington’s disease and multiple sclerosis, as well as the brain damage associated with stroke. In addition to the potential pathological relevance of adenosine receptors, there are earnest attempts in progress to generate ligands that will target adenosine receptors as therapeutic agents to treat some of these disorders.

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Abbreviations

ADAC:

Adenosine amine congener

AMP:

Adenosine monophosphate

AR:

Adenosine receptor

BDNF:

Brain-derived neurotrophic factor

BIIP20:

S-( − )-8-(3-Oxocyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione

cAMP:

Cyclic adenosine monophosphate

CCPA:

2-Chloro-N 6-cyclopentyladenosine

CGS15943:

5-Amino-9-chloro-2-(2-furyl)-1,2,4-triazolo[1,5-c]quinazoline

CGS21680:

2-[4-(2-Carboxyethyl)-phenylethylamino]-5′ N-ethyl-carbox amido-adenosine

CHA:

N 6-Cyclohexyladenosine

CJD:

Creutzfeldt–Jakob disease

Cl-IB-MECA:

2-Chloro-N 6-(3-iodobenzyl)adenosine-5′-N-methyluronamide

CNS:

Central nervous system

CP66,713:

4-Amino-1-phenyl[1,2,4]-triazolo[4,3-a]quinoxaline

CPA:

Cyclopentyl adenosine

8-CPT:

8-Cyclopentyltheophylline

CREB:

Cyclic AMP responsive element binding protein

CSC:

8-(3-Chloro styryl)caffeine

DMPX:

3,7-Dimethyl-1-propargylxanthine

DPCPX:

8-Cyclopentyl-1,3-dipropylxanthine

EAE:

Allergic encephalomyelitis

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

GABA:

Gamma-aminobutyric acid

HD:

Huntington’s disease

HGPRT:

Hypoxanthine-guanine phosphoribosyltransferase

IB–MECA:

N 6-(3-Iodobenzyl)adenosine-5′-N-methyluronamide

IL:

Interleukin

KFM19:

RS-( − )-8-(3-oxocyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione

LNS:

Lesch–Nyhan syndrome

MAP-2:

Microtubule-associated protein 2

MAPK:

Mitogen-activated protein kinases

MCAo:

Middle cerebral artery occlusion

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MRS2179:

N 6-Methyl-2′-deoxyadenosine-3′, 5′-bisphosphate

MRS1706:

N-(4-Acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- dipropyl-1H-purin-8-yl)-phenoxy]acetamide

MS:

Multiple sclerosis

NBTI:

Nitrobenzylthioinosine

NECA:

5′-N-Ethylcarboxamidoadenosine

NGF:

Nerve growth factor

NMDA:

N-Methyl-d-aspartate

3-NP:

3-Nitro-propionic acid

PKC:

Protein kinase C

PLC:

Phospholipase C

R-PIA:

R-Phenylisopropyladenosine

SAH:

S-Adenosylhomocysteine

SCH58261:

7-(2-Phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidine

TNF-α:

Tumor necrosis factor alpha

Trk:

Tropomyosin-related kinase

ZM241385:

4-(2-[7-Amino-2-(2-furyl)(1,2,4)-triazolo(2,3-a)-(1,3,5)triazin-5-yl-amino]ethyl)phenol

References

  • Abbracchio MP, Fogliatto G, Paoletti AM, Rovati GE, Cattabeni F (1992) Prolonged invitro exposure of rat-brain slices to adenosine-analogs: selective desensitization of adenosine-A(1) but not adenosine-A(2) receptors. Eur J Pharmacol 227:317–324

    Article  CAS  PubMed  Google Scholar 

  • Abbracchio MP, Rainaldi G, Giammarioli AM, Ceruti S, Brambilla R, Cattabeni F, Barbieri D, Franceschi C, Jacobson KA, Malorni W (1997) The A3 adenosine receptor mediates cell spreading, reorganisation of actin cytoskeleton and distribution of Bcl-x(L): studies in human astroglioma cells. Biochem Biophys Res Commun 241:297–304

    Article  CAS  PubMed  Google Scholar 

  • Abbracchio MP, Ceruti S, Brambilla R, Barbieri D, Camurri A, Franceschi C, Giammarioli AM, Jacobson KA, Cattabeni F, Malorni W (1998) Adenosine A3 receptors and viability of astrocytes. Drug Dev Res 45:379–386

    Article  CAS  Google Scholar 

  • Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58:281–341

    Article  CAS  PubMed  Google Scholar 

  • Aden U, Halldner L, Lagercrantz H, Dalmau I, Ledent C, Fredholm BB (2003) Aggravated brain damage after hypoxic ischemia in immature adenosine A(2A) knockout mice. Stroke 34: 739–744

    Article  PubMed  CAS  Google Scholar 

  • Albasanz JL, Perez S, Barrachina M, Ferrer I, Martin M (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer’s disease. Brain Pathol 18:211–219

    Article  CAS  PubMed  Google Scholar 

  • Alfinito PD, Wang SP, Manzino L, Rijhsinghani S, Zeevalk GD, Sonsalla PK (2003) Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively. J Neurosci 23:10982–10987

    CAS  PubMed  Google Scholar 

  • Andiné P, Rudolphi KA, Fredholm BB, Hagberg H (1990) Effect of propentofylline (HWA285) in extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. Br J Pharmacol 100:814–818

    PubMed  Google Scholar 

  • Angelucci ME, Cesário C, Hiroi RH, Rosalen PL, Da Cunha C (2002) Effects of caffeine on learning and memory in rats tested in the Morris water maze. Braz J Med Biol Res 35: 1201–1208

    Article  CAS  PubMed  Google Scholar 

  • Angulo E, Casado V, Mallol J, Canela EI, Vinals F, Ferrer I, Lluis C, Franco R (2003) A(1) adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation. Brain Pathol 13:440–451

    Article  CAS  PubMed  Google Scholar 

  • Appel E, Kazimirsky G, Ashkenazi E, Kim SG, Jacobson KA, Brodie C (2001) Roles of BCL-2 an caspase 3 in the adenosine A3 receptor-induced apoptosis. J Mol Neurosci 17:285–292

    Article  CAS  PubMed  Google Scholar 

  • Araki T, Kato H, Kanai Y, Kogure K (1993) Selective changes of neurotransmitter receptors in middle-aged gerbil brain. Neurochem Intern 23:541–548

    Article  CAS  Google Scholar 

  • Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 142:941–952

    Article  CAS  PubMed  Google Scholar 

  • Arvin B, Neville LF, Pan J, Roberts PJ (1989) 2-Chloroadenosine attenuates kainic acid-induced toxicity within the rat striatum: relationship to release of glutamate and Ca2 + influx. Br J Pharmacol 98:225–235

    CAS  PubMed  Google Scholar 

  • Baraldi PG, Tabrizi MA, Gessi S, Borea PA (2008) Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chem Rev 108:238–263

    Article  CAS  PubMed  Google Scholar 

  • Barnes CR, Mandell GL, Carper HT, Luong S, Sullivan GW (1995) Adenosine modulation of TNFα-induced neutrophil activation. Biochem Pharmacol 50:1851–1857

    Article  CAS  PubMed  Google Scholar 

  • Bartrup JT, Stone TW (1990) Activation of NMDA receptor-coupled channels suppresses the inhibitory action of adenosine on hippocampal slices. Brain Res 530:330–334

    Article  CAS  PubMed  Google Scholar 

  • Bartrup JT, Addae JI, Stone TW (1991) Interaction between adenosine and excitatory agonists in rat hippocampal slices. Brain Res 564:323–327

    Article  CAS  PubMed  Google Scholar 

  • Bauer A, Zilles K, Matusch A, Holzmann C, Riess O, von Horsten S (2005) Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington’s disease mutation. J Neurochem 94:639–650

    Article  CAS  PubMed  Google Scholar 

  • Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 321:168–171

    Article  CAS  PubMed  Google Scholar 

  • Beal MF, Ferrante RJ, Swartz KJ, Kowall NW (1991) Chronic quinolinic acid lesions in rats closely resemble Huntington’s disease. J Neurosci 11:1649–1659

    CAS  PubMed  Google Scholar 

  • Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002) Impaired glutamate transport and glutamate–glutamine cycling: downstream effects of the Huntington mutation. Brain 125:1908–1922

    Article  CAS  PubMed  Google Scholar 

  • Bensadoun JC, de Almeida LP, Dréano M, Aebischer P, Déglon N (2001) Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington’s syndrome. Eur J Neurosci 14:1753–1761

    Article  CAS  PubMed  Google Scholar 

  • Bertelli M, Cecchin S, Lapucci C, Jacomelli G, Jinnah HA, Pandolfo M, Micheli V (2006) Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch–Nyhan disease). Clin Chim Acta 373:104–107

    Article  CAS  PubMed  Google Scholar 

  • Bischofberger N, Jacobson KA, von Lubitz DKJE (1997) Adenosine A(1) receptor agonists as clinically viable agents for treatment of ischemic brain disorders. Ann NY Acad Sci 825:23–29

    Article  CAS  PubMed  Google Scholar 

  • Blum D, Gall D, Galas MC, d’Alcantara P, Bantubungi K, Schiffmann, SN (2002) The adenosine A(1) receptor agonist adenosine amine congener exerts a neuroprotective effect against the development of striatal lesions and motor impairments in the 3-nitropropionic acid model of neurotoxicity. J Neurosci 22:9122–9133

    CAS  PubMed  Google Scholar 

  • Blum D, Galas MC, Pintor A, Brouillet E, Ledent C, Muller CE, Bantubungi K, Galluzzo M, Gall D, Cuvelier L, Rolland AS, Popoli P, Schiffmann SN (2003a) A dual role of adenosine A(2A) receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A(2)A antagonists. J Neurosci 23:5361–5369

    CAS  PubMed  Google Scholar 

  • Blum D, Hourez R, Galas MC, Popoli P, Schiffmann SN (2003b) Adenosine receptors and Huntington’s disease: implications for pathogenesis and therapeutics. Lancet Neurol 2:366–374

    Article  CAS  PubMed  Google Scholar 

  • Bona E, Adén U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischaemia: the effect of adenosine receptor antagonists. Neuropharmacology 9:1327–1338

    Article  Google Scholar 

  • Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404

    Article  CAS  PubMed  Google Scholar 

  • Brambilla R, Cottini L, Fumagalli M, Ceruti S, Abbracchio MP (2003) Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia 43:190–194

    Article  PubMed  Google Scholar 

  • Bridges AJ, Bruns RF, Ortwine DF, Priebe SR, Szotek DL, Trivedi BK (1988) N 6-[2-(3,5-Dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine and its uronamide derivatives. Novel adenosine agonists and antagonists with both high affinity and high selectivity for the adenosine A2 receptor. J Med Chem 31:1282–1285

    Article  CAS  PubMed  Google Scholar 

  • Broadley KJ (2000) Drugs modulating adenosine receptors as potential therapeutic agents for cardiovascular diseases. Exp Opin Ther Pat 10:1669–1692

    Article  CAS  Google Scholar 

  • Brown SJ, James S, Reddington M, Richardson PJ (1990) Both A1 and A2A purine receptors regulate striatal acetylcholine release. J Neurochem 55:31–38

    Article  CAS  PubMed  Google Scholar 

  • Bullough DA, Magill MJ, Firestein GS, Mullane KM (1995) Adenosine activates A2 receptors to inhibit neutrophil adhesion and injury to isolated cardiac myocytes. J Immunol 155:2579–2586

    CAS  PubMed  Google Scholar 

  • Burkey TH, Webster RD (1993) Adenosine inhibits fMLP-stimulated adherence and superoxide anion generation by human neutrophils at an early step in signal transduction. Biochem Biophys Acta 1175:312–318

    Article  CAS  PubMed  Google Scholar 

  • Butcher SP, Bullock R, Graham DI, McCulloch J (1990) Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. Stroke 21:1727–1733

    CAS  PubMed  Google Scholar 

  • Cain BS, Meldrum DR, Dinarello CA, Meng X, Banerjee A, Harken AH (1998) Adenosine reduces cardiac TNF-α production and human myocardial injury following ischaemia-reperfusion. J Surg Res 76:117–123

    Article  CAS  PubMed  Google Scholar 

  • Canals M, Marcellino D, Fanelli F, Ciruela F, de Benedetti P, Goldberg SR, Neve K, Fuxe K, Agnati LF, Woods AS, Ferré S, Lluis C, Bouvier M, Franco R (2003) Adenosine A2A-dopamine D2 receptor–receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278:46741–46749

    Article  CAS  PubMed  Google Scholar 

  • Canals M, Angulo E, Casado V, Canela EI, Mallol J, Vinals F, Staines W, Tinner B, Hillion J, Agnati L, Fuxe K, Ferre S, Lluis C, Franco R (2005) Molecular mechanisms involved in the adenosine A(1) and A(2A) receptor-induced neuronal differentiation in neuroblastoma cells and striatal primary cultures. J Neurochem 92:337–348

    Article  CAS  PubMed  Google Scholar 

  • Cantor SL, Zornow MH, Miller LP, Yaksh TL (1992) The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. J Neurochem 59:1884–1892

    Article  CAS  PubMed  Google Scholar 

  • Cargnoni A, Ceconi C, Boraso A, Bernocchi P, Monopoli A, Curello S, Ferrari R (1999) Role of A2A receptors in the modulation of myocardial reperfusion damage. J Cardiovasc Pharmacol 33:883–893

    Article  CAS  PubMed  Google Scholar 

  • Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC (1999) Inflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 163:3963–3968

    CAS  PubMed  Google Scholar 

  • Casati C, Forlani A, Lozza G, Monopoli A (1997) Hemodynamic changes do not mediate the cardioprotection induced by the A1 adenosine receptor agonist CCPA in the rabbit. Pharmacol Res 35:51–55

    Article  CAS  PubMed  Google Scholar 

  • Cassada DC, Tribble CG, Kaza AK, Fiser SM, Long SM, Linden J, Rieger JM, Kron IL, Kern JA (2001a) Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery 130:230–235

    Article  CAS  PubMed  Google Scholar 

  • Cassada DC, Tribble CG, Laubach VE, Nguyen BN, Rieger JM, Linden J, Kaza AK, Long SM, Kron IL, Kern JA (2001b) An adenosine A(2A) agonist, ATL-146e, reduces paralysis and apoptosis during rabbit spinal cord reperfusion. J Vasc Surg 34:482–488

    Article  CAS  PubMed  Google Scholar 

  • Cassada DC, Tribble CG, Long SM, Laubach VE, Kaza AK, Linden J, Nguyen BN, Rieger JM, Fiser SM, Kron IL, Kern JA (2002) Adenosine A2(A) analogue ATL-146e reduces systemic tumor necrosing factor-α and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia. J Vasc Surg 35, 994–998

    Article  PubMed  Google Scholar 

  • Chen JF, Huang Z, Ma J, Zhu J, Moratalla R, Standaert D, Moskowitz MA, Fink JS, Schwarzschild MA (1999) A2A adenosine receptor deficiency attenuates brain injury induced by transient focal ischaemia in mice. J Neurosci 19:9192–9200

    CAS  PubMed  Google Scholar 

  • Chen G-J, Harvey BK, Shen H, Chou J, Victor A, Wang Y (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84:1848–1855

    Article  CAS  PubMed  Google Scholar 

  • Chiang MC, Lee YC, Huang CL, Chern YJ (2005) cAMP-response element-binding protein contributes to suppression of the A(2A) adenosine receptor promoter by mutant huntingtin with expanded polyglutamine residues. J Biol Chem 280:14331–14340

    Article  CAS  PubMed  Google Scholar 

  • Chou SY, Lee YC, Chen HM, Chiang MC, Lai HL, Chang HH, Wu YC, Sun CN, Chien CL, Lin YS, Wang SC, Tung YY, Chang C, Chern YJ (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury M, Fillenz M (1991) Presynaptic adenosine A2 and NMDA receptors regulate dopamine synthesis in rat striatal synaptosomes. J Neurochem 56:1783–1788

    Article  CAS  PubMed  Google Scholar 

  • Ciccarelli R, D’Alimonte I, Ballerini P, D’Auro M, Nargi E, Buccella S, Di Iorio P, Bruno V, Nicoletti F, Caciagli F (2007) Molecular signalling mediating the protective effect of A(1) adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol Pharmacol 71:1369–1380

    Article  CAS  PubMed  Google Scholar 

  • Coelho JE, Rebola N, Fragata I, Ribeiro JA, De Mendonca A, Cunha RA (2006) Hypoxia-induced desensitization and internalization of adenosine A(1) receptors in the rat hippocampus. Neuroscience 138:1195–1203

    Article  CAS  PubMed  Google Scholar 

  • Connick JH, Stone TW (1986) The effects of kainate, β-kainate and quinolinic acids on the release of endogenous amino acids from rat brain slices. Biochem Pharmacol 35:3631–3635

    Article  CAS  PubMed  Google Scholar 

  • Connick JH, Stone TW (1989) Quinolinic acid neurotoxicity: protection by intracerebral phenylisopropyl adenosine (PIA) and potentiation by hypotension. Neurosci Lett 101:191–196

    Article  CAS  PubMed  Google Scholar 

  • Corodimas KP, Tomita H (2001) Adenosine A1 receptor activation selectively impairs the acquisition of contextual fear conditioning in rats. Behav Neurosci 115(6):1283–1290

    Article  CAS  PubMed  Google Scholar 

  • Corradetti R, Lo Conte G, Moroni F, Passani MB, Pepeu G (1984) Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol 140:19–26

    Article  Google Scholar 

  • Corset V, Nguyen-Ba-Charvet KT, Forcet C, Moyse E, Chetodal, A, Mehlen P (2000) Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2B receptor. Nature 407:747–750

    Article  CAS  PubMed  Google Scholar 

  • Corsi C, Melani A, Bianchi L, Pepeu G, Pedata F (1999a) Striatal A2A adenosine receptors differentially regulate spontaneous and K + -evoked glutamate release in vivo in young and aged rats. Neuroreport 10:687–691

    CAS  PubMed  Google Scholar 

  • Corsi C, Melani A, Bianchi L, Pepeu G, Pedata F (1999b) Effect of adenosine A2A stimulation on GABA release from the striatum of young and aged rats in vivo. Neuroreport 10:3933–3937

    CAS  PubMed  Google Scholar 

  • Corsi C, Melani A, Bianchi L, Pedata F (2000) Striatal A2A adenosine receptor antagonism differentially modifies striatal glutamate outflow in vivo in young and aged rats. Neuroreport 11:2591–2595

    Article  CAS  PubMed  Google Scholar 

  • Coyle JT, Schwarcz R (1976) Lesion of striatal neurones with kainic acid provides a model for Huntington’s chorea. Nature 263:244–246

    Article  CAS  PubMed  Google Scholar 

  • Cronstein BN (1994) Adenosine, an endogenous anti-inflammatory agent. J Appl Physiol 76:5–13

    CAS  PubMed  Google Scholar 

  • Cronstein BN, Rosenstein ED, Kramer SB, Weissmann G, Hirschhorn R (1985) Adenosine: a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 135:1366–1371

    CAS  PubMed  Google Scholar 

  • Cronstein BN, Kubersky SM, Weissmann G, Hirschhorn R (1987) Engagement of adenosine receptors inhibits hydrogen peroxide-release by activated human neutrophils. Clin Immunol Immunopathol 42:76–85

    Article  CAS  PubMed  Google Scholar 

  • Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M (1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that both promote chemotaxis and inhibit O2 generation respectively. J Clin Invest 85:1150–1157

    Article  CAS  PubMed  Google Scholar 

  • Cronstein BN, Levin RI, Philips M, Hirschhorn R, Abramson SB, Weissmann G (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 148:2201–2206

    CAS  PubMed  Google Scholar 

  • Cunha RA, Johansson B, van der Ploeg I, Sebastião AM, Ribeiro JA, Fredholm BB (1994) Evidence for functionally important adenosine A2a receptors in the rat hippocampus. Brain Res 649:208–216

    Article  CAS  PubMed  Google Scholar 

  • Cunha RA, Constantino MC, Sebastião AM, Ribeiro JA (1995) Modification of A1 and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat. Neuroreport 6:1583–1588

    Article  CAS  PubMed  Google Scholar 

  • Cunha RA, Johansson B, Constantino MD, Sebastião AM, Fredholm BB (1996) Evidence for high affinity binding sites for the adenosine A2A receptor agonist [3H]CGS21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors. Naunyn–Schmiedeberg’s Arch Pharmacol 353:261–271

    Article  CAS  Google Scholar 

  • D’Alimonte I, Ballerini P, Nargi E, Buccella S, Giuliani P, Di Iorio P, Caciagli, F (2007) Staurosporine-induced apoptosis in astrocytes is prevented by A(1) adenosine receptor activation. Neurosci Lett 418:66–71

    Article  PubMed  CAS  Google Scholar 

  • Dall’lgna OP, Porciuncula LO, Souza DO, Cunha RA, Lara DR (2003) Neuroprotection by caffeine and adenosine A(2A) receptor blockade of β-amyloid neurotoxicity. Br J Pharmacol 138: 1207–1209

    Article  PubMed  CAS  Google Scholar 

  • Dall’Igna OP, Fett P, Gomes MW, Souza DO, Cunha RA, Lara DR (2007) Caffeine and adenosine A(2a) receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice. Exp Neurol 203:241–245

    Article  PubMed  CAS  Google Scholar 

  • Deckert J, Abel F, Kunig G, Hartmann J, Senitz D, Maier H, Ransmayr G, Riederer P (1998) Loss of human hippocampal adenosine A(1) receptors in dementia: evidence for lack of specificity. Neurosci Lett 244:1–4

    Article  CAS  PubMed  Google Scholar 

  • De Mendonca A, Sebastiao AM, Ribeiro JA (1995) Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal-neurons by adenosine A(1) receptor activation. Neuroreport 6:1097–1100

    Article  PubMed  Google Scholar 

  • Dianzani C, Brunelleschi S, Viano I, Fantozzi R (1994) Adenosine modulation of primed human neutrophils. Eur J Pharmacol 263:223–226

    Article  CAS  PubMed  Google Scholar 

  • Di-Capua N, Sperling O, Zoref-Shani E (2003) Protein kinase C-epsilon is involved in the adenosine-activated signal transduction pathway conferring protection against ischemia-reperffision injury in primary rat neuronal cultures. J Neurochem 84:409–412

    Article  CAS  PubMed  Google Scholar 

  • Di Iorio P, Kleywegt S, Ciccarelli R, Traversa U, Andrew CM, Crocker CE, Werstiuk ES, Rathbone MP (2002) Mechanisms of apoptosis induced by purine nucleosides in astrocytes. Glia 38: 179–190

    Article  PubMed  Google Scholar 

  • Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468

    CAS  PubMed  Google Scholar 

  • Dixon AK, Widdowson L, Richardson PJ (1997) Desensitisation of the adenosine A1 receptor by the A2A receptor in the rat striatum. J Neurochem 69:315–321

    Article  CAS  PubMed  Google Scholar 

  • Dolphin AC, Prestwich SA (1985) Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature 316:148–150

    Article  CAS  PubMed  Google Scholar 

  • Domenici MR, Scattoni ML, Martire A, Lastoria G, Potenza RL, Borioni A, Venerosi A, Calamandrei G, Popoli P (2007) Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH58261 in R6/2 Huntington’s disease mice. Neurobiol Disease 28:197–205

    Article  CAS  Google Scholar 

  • Dux E, Fastbom J, Ungerstedt U, Rudolphi K, Fredholm BB (1990) Protective effect of adenosine and a novel xanthine derivative propentofylline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res 516:248–256

    Article  CAS  PubMed  Google Scholar 

  • Evans MC, Swan JH, Meldrum BS (1987) An adenosine analog, 2-chloroadenosine, protects against long-term development of ischemic cell loss in the rat hippocampus. Neurosci Lett 83:287–292

    Article  CAS  PubMed  Google Scholar 

  • Ezeamuzie CI, Philips E (1999) Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. Br J Pharmacol 127:188–194

    Article  CAS  PubMed  Google Scholar 

  • Fastbom J, Fredholm BB (1985) Inhibition of (3H)glutamate release from rat hippocampal slices by L-PIA. Acta Physiol Scand 125:121–123

    Article  CAS  PubMed  Google Scholar 

  • Fastbom J, Pazos A, Probst A, Palacios JM (1986) Adenosine A1-receptors in human brain: characterisation and autoradiographic visualisation. Neurosci Lett 65:127–132

    Article  CAS  PubMed  Google Scholar 

  • Fastbom J, Pazos A, Palacios JM (1987a) The distribution of adenosine A1 receptors and 5′-nucleotidase in the brain of some commonly used experimental animals. Neuroscience 22:813–826

    Article  CAS  PubMed  Google Scholar 

  • Fastbom J, Pazos A, Probst A, Palacios JM (1987b) Adenosine A1 receptors in the human brain: a quantitative autoradiographic study. Neuroscience 22:827–839

    Article  CAS  PubMed  Google Scholar 

  • Fedorova IM, Jacobson MA, Basile A, Jacobson KA (2003) Behavioral characterization of mice lacking the A(3) adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol 23:431–447

    Article  CAS  PubMed  Google Scholar 

  • Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298:757–759

    Article  CAS  PubMed  Google Scholar 

  • Ferrante RJ, Kowall NW, Cipolloni PB, Storey E, Beal MF (1993) Excitotoxin lesions in primates as a model for Huntington’s disease: histopathologic and neurochemical characterization. Exp Neurol 119:46–71

    Article  CAS  PubMed  Google Scholar 

  • Ferré S, von Euler G, Johansson B, Fredholm BB, Fuxe K (1991) Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Natl Acad Sci U S A 88:7238–7241

    Article  PubMed  Google Scholar 

  • Fiebich BL, Biber K, Gyufko K, Berger R, Bauer J, vanCalker D (1996a) Adenosine A(2b) receptors mediate an increase in interleukin (IL)-6 mRNA and IL-6 protein synthesis in human astroglioma cells. J Neurochem 66:1426–1431

    Article  CAS  PubMed  Google Scholar 

  • Fiebich BL, Biber K, Lieb K, vanCalker D, Berger M, Bauer J, GebickeHaerter PJ (1996b) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A(2a)-receptors. Glia 18:152–160

    Article  CAS  PubMed  Google Scholar 

  • Fiebich BL, Akundi RS, Biber K, Hamke M, Schmidt C, Butcher RD, van Calker D, Willmroth F (2005) IL-6 expression induced by adenosine A(2b) receptor stimulation in U373MG cells depends on p38 mitogen activated kinase and protein kinase C. Neurochem Intern 46:501–512

    Article  CAS  Google Scholar 

  • Fink JS, Kalda A, Ryu H, Stack EC, Schwarzschild MA, Chen JF, Ferrante RJ (2004) Genetic and pharmacological inactivation of the adenosine A(2A) receptor attenuates 3-nitropropionic acid-induced striatal damage. J Neurochem 88:538–544

    Article  CAS  PubMed  Google Scholar 

  • Finn SF, Swartz KJ, Beal MF (1991) 2-Chloroadenosine attenuates NMDA, kainate and quisqualate toxicity. Neurosci Lett 126:191–194

    Article  CAS  PubMed  Google Scholar 

  • Fotheringham J, Mayne M, Holden C, Nath A, Geiger JD (2004) Adenosine receptors control HIV-1 Tat-induced inflammatory responses through protein phosphatase. Virology 327:186–195

    Article  CAS  PubMed  Google Scholar 

  • Fredholm BB, Dunwiddie TV (1988) How does adenosine inhibit transmitter release? Trends Pharmacol Sci 9:130–134

    Article  CAS  PubMed  Google Scholar 

  • Fredholm BB, Johansson B, Lindstrom K, Wahlstrom G (1998) Age-dependent changes in adenosine receptors are not modified by life-long intermittent alcohol administration. Brain Res 791:177–185

    Article  CAS  PubMed  Google Scholar 

  • Gao Y, Phillis JW (1994) CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. Life Sci 55:PL61–PL65

    Article  CAS  PubMed  Google Scholar 

  • Gerevich Z, Wirkner K, Illes P (2002) Adenosine A(2A) receptors inhibit the N-methyl-D-aspartate component of excitatory synaptic currents in rat striatal neurons. Eur J Pharmacol 451:161–164

    Article  CAS  PubMed  Google Scholar 

  • Gianfriddo M, Melani A, Turchi D, Giovannini MG, Pedata F (2004) Adenosine and glutamate extracellular concentrations and mitogen-activated protein kinases in the striatum of Huntington transgenic mice. Selective antagonism of adenosine A(2A) receptors reduces transmitter outflow. Neurobiol Dis 17:77–88

    Article  CAS  PubMed  Google Scholar 

  • Giménez-Llort L, Fernández-Teruel A, Escorihuela RM, Fredholm BB, Tobeña A, Pekny M, Johansson B (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16:547–550

    Article  PubMed  Google Scholar 

  • Goncalves ML, Cunha RA, Ribeiro JA (1997) Adenosine A2A receptors facilitate 45Ca2 + uptake through class A calcium channels in rat hippocampal CA3 but not CA1 synaptosomes. Neurosci Lett 238:73–77

    Article  CAS  PubMed  Google Scholar 

  • Goodman RR, Snyder SH (1982) Autoradiographic localisation of adenosine receptors in rat brain using [3H]cyclohexyladenosine. J Neurosci 2:1230–1241

    CAS  PubMed  Google Scholar 

  • Graham SH, Chen J, Sharp FR, Simon RP (1993) Limiting ischaemic injury by inhibition of excitatory amino acid release. J Cereb Blood Flow Metab 13:88–97

    CAS  PubMed  Google Scholar 

  • Grisham MB, Hernandez LA, Granger DN (1989) Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation. Am J Physiol 257:H1334–H1339

    CAS  PubMed  Google Scholar 

  • Grondin R, Bédard PJ, Hadj Tahar A, Grégoire L, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52:1673–1677

    CAS  PubMed  Google Scholar 

  • Guidetti P, Luthi-Carter RE, Augood SJ, Schwarcz R (2004) Neostriatal and cortical quinolinate levels are increased in early grade Huntington’s disease. Neurobiol Dis 17:455–461

    Article  CAS  PubMed  Google Scholar 

  • Hannon JP, Bray-French KM, Phillips RM, Fozard JR (1998) Further pharmacological characterization of the adenosine receptor subtype mediating inhibition of oxidative burst in human isolated neutrophils. Drug Dev Res 43:214–224

    Article  CAS  Google Scholar 

  • Hara H, Onodera H, Kato H, Kogure K (1992) Effects of aging on signal transmission and transduction systems in the gerbil brain: morphological and autoradiographic study. Neuroscience 46:475–488

    Article  CAS  PubMed  Google Scholar 

  • Haskó G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25(1):33–39

    Article  PubMed  CAS  Google Scholar 

  • Haskó G, Németh ZH, Vizi ES, Salzman AL, Szabó C (1998) An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur J Pharmacol 358:261–268

    Article  PubMed  Google Scholar 

  • Haskó G, Pacher P, Deitch EA, Vizi ES (2007) Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 113:264–275

    Article  PubMed  CAS  Google Scholar 

  • Hauber W, Bareiss A (2001) Facilitative effects of an adenosine A1∕A2 receptor blockade on spatial memory performance of rats: selective enhancement of reference memory retention during the light period. Behav Brain Res 118(1):43–52

    Article  CAS  PubMed  Google Scholar 

  • Heese K, Fiebich BL, Bauer J, Otten U (1997) Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A(2a)-receptors. Neurosci Lett 231:83–86

    Article  CAS  PubMed  Google Scholar 

  • Héron A, Lasbennes F, Seylez J (1993) Adenosine modulation of amino acid release in rat hippocampus during ischaemia and veratridine depolarisation. Brain Res 608:27–32

    Article  PubMed  Google Scholar 

  • Héron A, Lekieffre D, Le Peillet E, Lasbennes F, Seylaz J, Plotkine M, Boulu RG (1994) Effects of an A1 adenosine receptor agonist on the neurochemical, behavioural and histological consequences of ischaemia. Brain Res 641:217–224

    Article  PubMed  Google Scholar 

  • Hiraide T, Katsura K, Muramatsu H, Asano G, Katayama Y (2001) Adenosine receptor antagonists cancelled the ischemic tolerance phenomenon in gerbil. Brain Res 910:94–98

    Article  CAS  PubMed  Google Scholar 

  • Hollins C, Stone TW (1980) Adenosine inhibition of GABA release from slices of rat cerebral cortex. Br J Pharmacol 69:107–112

    CAS  PubMed  Google Scholar 

  • Hooper N, Fraser C, Stone TW (1996) Effects of purine analogues on spontaneous alternation in mice. Psychopharmacology 123(3):250–257

    Article  CAS  PubMed  Google Scholar 

  • Hosseinzadeh H, Stone TW (1998) Tolbutamide blocks postsynaptic but not presynaptic effects of adenosine on hippocampal CA1 neurons. J Neural Transm 105:161–172

    Article  CAS  PubMed  Google Scholar 

  • Huang QY, Wei C, Yu LQ, Coelho JE, Shen HY, Kalda A, Linden J, Chen JF (2006) Adenosine A2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-type-selective inactivation. J Neurosci 26:11371–11378

    Article  CAS  PubMed  Google Scholar 

  • Hutchison AJ, Webb RL, Oei HH, Ghai GR, Zimmerman MB, Williams M (1989) CGS21680, an A2 selective adenosine receptor agonist with preferential hypotensive activity. J Pharmacol Exp Ther 251:47–55

    CAS  PubMed  Google Scholar 

  • Ikeda M, Mackay KB, Dewar D, Mcculloch J (1993) Differential alterations in adenosine-A(1) and kappa-1-opioid receptors in the striatum in Alzheimer’s-disease. Brain Res 616:211–217

    Article  CAS  PubMed  Google Scholar 

  • Jaarsma D, Sebens JB, Korf J (1991) Reduction of adenosine-A1-receptors in the perforant pathway terminal zone in Alzheimer hippocampus. Neurosci Lett 121:111–114

    Article  CAS  PubMed  Google Scholar 

  • Jacobson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19:184–191

    Article  CAS  PubMed  Google Scholar 

  • Jacobson I, Hamberger A (1985) Kainic acid-induced changes of extracellular amino acid levels, evoked potentials and EEG activity in the rabbit olfactory bulb. Brain Res 348:289–296

    Article  CAS  PubMed  Google Scholar 

  • Jansen KLR, Faull RLM, Dragunow M, Synek BL (1990) Alzheimer’s disease: changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors—an autoradiographic study. Neuroscience 39:613–627

    Article  CAS  PubMed  Google Scholar 

  • Jarvis MF, Williams M (1989) Direct autoradiographic localisation of adenosine A2 receptors in the brain using the A2-selective agonist, [3H]CGS21680. Eur J Pharmacol 168:243–246

    Article  CAS  PubMed  Google Scholar 

  • Jiang N, Kowaluk EA, Lee CH, Mazdiyasni H, Chopp M (1997) Adenosine kinase inhibition protects brain against transient focal ischemia in rats. Eur J Pharmacol 320:131–137

    Article  CAS  PubMed  Google Scholar 

  • Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D (2002) Coffee consumption and cognitive function among older adults. Am J Epidemiol 156:842–850

    Article  PubMed  Google Scholar 

  • Johnston JB, Silva C, Gonzalez G, Holden J, Warren KG, Metz LM, Power C (2001) Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Ann Neurol 49:650–658

    Article  CAS  PubMed  Google Scholar 

  • Jones PA, Smith RA, Stone TW (1998a) Protection against intrahippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800: 328–335

    Article  CAS  PubMed  Google Scholar 

  • Jones PA, Smith RA, Stone TW (1998b) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85:229–237

    Article  CAS  PubMed  Google Scholar 

  • Kalaria RN, Sromek S, Wilcox BJ, Unnerstall JR (1990) Hippocampal adenosine-A1-receptors are decreased in Alzheimer’s-disease. Neurosci Lett 118:257–260

    Article  CAS  PubMed  Google Scholar 

  • Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner P (1998) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43:507–513

    Article  CAS  PubMed  Google Scholar 

  • Kano T, Katayama Y, Kawamata T, Hirota H, Tsubokawa T (1994) Propentofylline administered by microdialysis attenuates ischaemia-induced hippocampal damage but not excitatory amino acid release in gerbils. Brain Res 641:149–154

    Article  CAS  PubMed  Google Scholar 

  • Khaspekov L, Shamloo M, Victorov I, Wieloch T (1998) Sublethal in vitro glucose-oxygen deprivation protects cultured hippocampal neurons against a subsequent severe insult. Neuroreport 9:1273–1276

    Article  CAS  PubMed  Google Scholar 

  • Knutsen LJS, Sheardown MJ, Roberts SM, Mogensen JP, Olsen UB, Thomsen C, Bowler AN (1998) Adenosine A1 and A3 selective N-alkoxypurines as novel cytokine modulators and neuroprotectants. Drug Dev Res 45:214–221

    Article  CAS  Google Scholar 

  • Kohler C, Schwarcz R, Fuxe K (1978) Perforant path transections protect hippocampal granule cells from kainate lesion. Neurosci Lett 10:241–246

    Article  CAS  PubMed  Google Scholar 

  • Kopf SR, Melani A, Pedata F, Pepeu G (1999) Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists. Psychopharmacology 146:214–219

    Article  CAS  PubMed  Google Scholar 

  • Kreckler LM, Wan TC, Ge ZD, Auchampach JA (2006) Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A(2A) and A(2B) but not the A(3) adenosine receptor. J Pharmacol Exp Ther 317:172–180

    Article  CAS  PubMed  Google Scholar 

  • Kurokawa M, Kirk IP, Kirkpatrick KA, Kase H, Richardson PJ (1994) Inhibition by KF17837 of adenosine A2A receptor-mediated modulation of striatal GABA and acetylcholine release. Br J Pharmacol 113:43–48

    CAS  PubMed  Google Scholar 

  • Lai DM, Tu YK, Liu IM, Cheng JT (2005) Increase of adenosine A1 receptor gene expression in cerebral ischemia of Wistar rats. Neurosci Lett 387:59–61

    Article  CAS  PubMed  Google Scholar 

  • Lappin D, Whaley K (1984) Adenosine A2 receptors on human monocytes modulate C2 production. Clin Exp Immunol 57:454–460

    CAS  PubMed  Google Scholar 

  • Latini S, Pazzagli M, Pepeu G, Pedata F (1996) A2 adenosine receptors: their presence and neuromodulatory role in the CNS. Gen Pharmacol 27:925–933

    CAS  PubMed  Google Scholar 

  • Latini S, Bordoni F, Corradetti R, Pepeu G, Pedata F (1999) Effect of A2A adenosine receptor stimulation and antagonism on synaptic depression induced by in vitro ischaemia in rat hippocampal slices. Br J Pharmacol 128:1035–1044

    Article  CAS  PubMed  Google Scholar 

  • Lau Y-S, Mouradian MM (1993) Protection against acute MPT-induced dopamine depletion in mice by adenosine. J Neurochem 60:768–771

    Article  CAS  PubMed  Google Scholar 

  • Lee FS, Chao MV (2001) Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 98:3555–3560

    Article  CAS  PubMed  Google Scholar 

  • Lee KS, Reddington M (1986) Autoradiographic evidence for multiple CNS binding sites for adenosine derivative. Neuroscience 19:535–549

    Article  CAS  PubMed  Google Scholar 

  • Lehmann A, Isacsson H, Hamberger A (1983) Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. J Neurochem 40:1314–1320

    CAS  PubMed  Google Scholar 

  • LeVraux V, Chen YL, Masson I, De Sousa M, Giroud JP, Florentin I, Chauvelot-Moachon L (1993) Inhibition of human monocyte TNF production by adenosine receptor agonists. Life Sci 52:1917–1924

    Article  CAS  Google Scholar 

  • Li XX, Nomura T, Aihara H, Nishizaki T (2001) Adenosine enhances glial glutamate efflux via A2A adenosine receptors. Life Sci 68:1343–1350

    Article  CAS  PubMed  Google Scholar 

  • Linden J, Thai T, Figler H, Jin X, Robeva AS (1999) Characterization of human A2B adenosine receptors: radioligand binding, western blotting, and coupling to Gq in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol 56:705–713

    CAS  PubMed  Google Scholar 

  • Link AA, Kino T, Worth JA, McGuire JL, Crane ML, Chrousos GP, Wilder RL, Elenkov IJ (2000) Ligand activation of the adenosine A2A receptors inhibits IL-12 production by human monocytes. J Immunol 164:436–442

    CAS  PubMed  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622

    Article  CAS  PubMed  Google Scholar 

  • Liu HC, Hon CJ, Liu TY, Tsai, SJ (2005) Association analysis of adenosine A2a receptor 1976T > C polymorphisms and Alzheimer’s disease. Eur Neurol 53:99–100

    Article  PubMed  Google Scholar 

  • Liu YH, Xiong L, Chen SY, Wang Q (2006) Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A(1) receptor antagonists. Can J Anaes 53:194–201

    Article  Google Scholar 

  • Lozza G, Conti A, Ongini E, Monopoli A (1997) Cardioprotective effects of adenosine A1 and A2A receptor agonists in the isolated heart. Pharmacol Res 35:57–64

    Article  CAS  PubMed  Google Scholar 

  • MacGregor DG, Stone TW (1993) Inhibition by the adenosine analogue, (R)-N 6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration. Br J Pharmacol 109:316–321

    CAS  PubMed  Google Scholar 

  • MacGregor DG, Miller WJ, Stone TW (1993) Mediation of the neuroprotective action of R-phenylisopropyladenosine through a centrally located adenosine A1 receptor. Br J Pharmacol 110:470–476

    CAS  PubMed  Google Scholar 

  • MacGregor DG, Jones PA, Maxwell WL, Graham DI, Stone TW (1996) Prevention by a purine analogue of kainate-induced neuropathology in rat hippocampus. Brain Res 725:115–120

    CAS  PubMed  Google Scholar 

  • Maemoto T, Tada M, Mihara T, Ueyama N, Matsuoka H, Harada K, Yamaji T, Shirakawa K, Kuroda S, Akahane A, Iwashita A, Matsuoka N, Mutoh S (2004) Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine A(1) receptors. J Pharmacol Sci 96:42–52

    Article  CAS  PubMed  Google Scholar 

  • Mager R, Ferroni S, Schubert P (1990) Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons. Brain Res 532:58–62

    Article  CAS  PubMed  Google Scholar 

  • Maggirwar SB, Dhanraj DN, Somani SM, Ramkumar V (1994) Adenosine acts as an endogenous activator of the cellular antioxidant defense system. Biochem Biophys Res Commun 201: 508–515

    Article  CAS  PubMed  Google Scholar 

  • Maglione V, Giallonardo P, Cannella M, Martino T, Frati L, Squitieri F (2005) Adenosine A(2A) receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington’s disease. Am J Med Genet B Neuropsychiatr Genet 139B:101–105

    Article  CAS  PubMed  Google Scholar 

  • Maglione V, Cannella M, Martino T, De Blasi A, Frati L, Squitieri F (2006) The platelet maximum number of A2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington’s disease patients with predominant chorea. Neurosci Lett 393:27–30

    Article  CAS  PubMed  Google Scholar 

  • Maia L, de Mendonça A (2002) Does caffeine intake protect from Alzheimer’s disease? Eur J Neurol 9:377–382

    Article  CAS  PubMed  Google Scholar 

  • Mally J, Stone TW (1994) The effect of theophylline on parkinsonian symptoms. J Pharm Pharmacol 46:515–517

    CAS  PubMed  Google Scholar 

  • Mally J, Stone TW (1996) Potential role of adenosine antagonist therapy in pathological tremor disorders. Pharmacol Ther 72:243–250

    Article  CAS  PubMed  Google Scholar 

  • Mally J, Stone TW (1998) Potential of adenosine A(2A) receptor antagonists in the treatment of movement disorders. CNS Drugs 10:311–320

    Article  CAS  Google Scholar 

  • Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier T, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localisation in the human basal ganglia and alterations with disease. Neuroscience 42:697–706

    Article  CAS  PubMed  Google Scholar 

  • Matherne GP, Linden J, Byford AM, Gauthier NS, Headrick JP (1997) Transgenic A1 adenosine receptor overexpression increases myocardial resistance to ischaemia. Proc Nat Acad Sci USA 94:6541–6546

    Article  CAS  PubMed  Google Scholar 

  • Mayfield RD, Suzuki F, Zahniser NR (1993) Adenosine A2A receptor modulation of electrically evoked endogenous GABA release from rat globus pallidus. J Neurochem 60:2334–2337

    Article  CAS  PubMed  Google Scholar 

  • Mayne M, Shepel PN, Jiang Y, Geiger JD, Power C (1999) Dysregulation of adenosine A(1) receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol 45:633–639

    Article  CAS  PubMed  Google Scholar 

  • McLarnon JG, Choi HB, Lue LF, Walker DG, Kim SU (2005) Perturbations in calcium-mediated signal transduction in microglia from Alzheimer’s disease patients. J Neurosci Res 81:426–435

    Article  CAS  PubMed  Google Scholar 

  • McRae A, Rudolphi KA, Schubert P (1994) Propentofylline depresses amyloid and Alzheimer’s CSF microglial antigens after ischaemia. Neuroreport 5:1193–1196

    CAS  PubMed  Google Scholar 

  • McWhinney CD, Dudley MW, Bowlin TL, Peet NP, Schook L, Bradshaw M, De M, Borcherding DR, Edwards CK 3rd (1996) Activation of adenosine A3 receptors on macrophages inhibits TNFα. Eur J Pharmacol 310:209–216

    Article  CAS  PubMed  Google Scholar 

  • Meerlo P, Roman V, Farkas E, Keijser JN, Nyakas C, Luiten PGM (2004) Ageing-related decline in adenosine A1 receptor binding in the rat brain: an autoradiographic study. J Neurosci Res 78:742–748

    Article  CAS  PubMed  Google Scholar 

  • Meiners I, Hauschildt S, Nieber K, Munch G (2004) Pentoxyphylline and propentophylline are inhibitors of TNF-ot release in monocytes activated by advanced glycation endproducts. J Neural Transm 111:441–447

    Article  CAS  PubMed  Google Scholar 

  • Melani A, Pantoni L, Corsi C, Bianchi L, Monopoli A, Bertorelli R, Pepeu G, Pedata F (1999) Striatal outflow of adenosine, excitatory amino acids, GABA, and taurine in awake, freely moving rats after middle cerebral artery occlusion: correlation with neurological deficit and histopathological damage. Stroke 30:2448–2454

    CAS  PubMed  Google Scholar 

  • Meldrum DR, Cain BS, Cleveland JC Jr, Meng X, Ayala A, Banerjee A, Harken AH (1997) Adenosine decreases post-ischemic cardiac TNF-α production: anti-inflammatory implications for preconditioning and transplantation. Immunology 92:472–477

    Article  CAS  PubMed  Google Scholar 

  • Merkel LA, Lappe RW, Rivera LM, Cox BF, Perrone MH (1992) Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. J Pharmacol Exp Ther 260:437–443

    CAS  PubMed  Google Scholar 

  • Michaelis ML, Michaelis EK, Myers SL (1979) Adenosine modulation of synaptosomal dopamine release. Life Sci 24:2083–2092

    Article  CAS  PubMed  Google Scholar 

  • Mielke R, Kessler J, Szelies B, Herholz K, Wienhard K, Heiss WD (1996a) Vascular dementia: perfusional and metabolic disturbances and effects of therapy. J Neural Transm 47:183–191

    CAS  Google Scholar 

  • Mielke R, Kittner B, Ghaemi M, Kessler J, Szelies B, Herholz K, Heiss WD (1996b) Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia. J Neurol Sci 141:59–64

    Article  CAS  PubMed  Google Scholar 

  • Miller WJ, Macgregor DG, Stone TW (1994) Time-course of purine protection against kainate-induced increase in hippocampal [H-3] PK11195 binding. Brain Res Bull 34:133–136

    Article  CAS  PubMed  Google Scholar 

  • Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of adenosine A2A receptors by SCH58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport 9:3955–3959

    Article  CAS  PubMed  Google Scholar 

  • Moreau JL, Huber G (1999) Central adenosine A2A receptors: an overview. Brain Res Rev 31: 65–82

    Article  CAS  PubMed  Google Scholar 

  • Moreno MB, Hevia H, Santamaria M, Sepulcre J, Munoz J, Garcia-Trevijano ER, Berasain C, Corrales FJ, Avila MA, Villoslada P (2006) Methylthioadenosine reverses brain autoimmune disease. Ann Neurol 60:323–334

    Article  CAS  PubMed  Google Scholar 

  • Muller CE (1997) A(1)-adenosine receptor antagonists. Exp Opin Ther Pat 7:419–440

    Article  CAS  Google Scholar 

  • Muller CE (2000) A(2A) adenosine receptor antagonists—future drugs for Parkinson’s disease? Drugs Future 25:1043–1052

    Article  CAS  Google Scholar 

  • Murray TF (1982) Up-regulation of rat cortical adenosine receptors following chronic administration of theophylline. Eur J Pharmacol 82:113–114

    Article  CAS  PubMed  Google Scholar 

  • Nakamura M, Nakakimura K, Matsumoto M, Sakabe T (2002) Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A(1) receptor antagonist. J Cereb Blood Flow Metab 22:161–170

    Article  CAS  PubMed  Google Scholar 

  • Nakata H, Yoshioka K, Saitoh O (2003) Hetero-oligomerization between adenosine A1 and P2Y1 receptors in living cells: formation of ATP-sensitive adenosine receptors. Drug Dev Res 58:340–349

    Article  CAS  Google Scholar 

  • Nikbakht M-R, Stone TW (2001) Activation of NMDA receptors suppresses the presynaptic effects of adenosine. Br J Pharmacol 133:155P

    Google Scholar 

  • Nishizaki T (2004) ATP- and adenosine-mediated signaling in the central nervous system: adenosine stimulates glutamate release from astrocytes via A2A adenosine receptors J Pharmacol Sci 94:100–102

    Google Scholar 

  • Nishizaki T, Nagai K, Nomura T, Tada H, Kanno T, Tozaki H, Li XX, Kondoh T, Kodama N, Takahashi E, Sakai N, Tanaka K, Saito N (2002) A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors. Glia 39:133–47

    Article  CAS  PubMed  Google Scholar 

  • Noble S, Wagstaff AJ (1997) Propentofylline. CNS Drugs 8:257–264

    Article  CAS  Google Scholar 

  • Norenberg W, Wirkner K, Illes P (1997) Effect of adenosine and some of its structural analogues on the conductance of NMDA receptor channels in a subset of rat neostriatal neurones. Br J Pharmacol 122:71–80

    Article  CAS  PubMed  Google Scholar 

  • Norenberg W, Wirkner K, Assmann H, Richter M, Illes P (1998) Adenosine A(2A) receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons. Aminoacids 14:33–39

    CAS  Google Scholar 

  • Normile HJ, Barraco RA (1991) N 6-Cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors. Brain Res Bull 27:101–104

    Article  CAS  PubMed  Google Scholar 

  • O’Kane EM, Stone TW (1998) Interactions between A1 and A2 adenosine receptor-mediated responses in the rat hippocampus in vitro. Eur J Pharmacol 362:17–25

    Article  PubMed  Google Scholar 

  • O’Regan MH, Simpson RE, Perkins LM, Phillis JW (1992) The selective A2 adenosine receptor agonist CGS21680 enhances excitatory amino acid release from the ischaemic rat cerebral cortex. Neurosci Lett 138:169–172

    Article  PubMed  Google Scholar 

  • Ochiishi T, Chen L, Yukawa A, Saitoh Y, Sekino Y, Arai T, Nakata H, Miyamoto H (1999a) Cellular localisation of adenosine A1 receptors in rat forebrain: immunohistochemical analysis using adenosine A1 receptor-specific monoclonal antibody. J Comp Neurol 411:301–316

    Article  CAS  PubMed  Google Scholar 

  • Ochiishi T, Saitoh Y, Yukawa A, Saji M, Ren Y, Shirao T, Miyamoto H, Nakata H, Sekino Y (1999b) High levels of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus. Neuroscience 93:955–967

    Article  CAS  PubMed  Google Scholar 

  • Ochoa CM, Jackson TA, Aaron CS, Lahti RA, Strain GM, Von Voigtlander PF (1992) Antagonism of kainic acid lesions in the mouse hippocampus by U-54494A and U-50488H. Life Sci 51:1135–1143

    Article  CAS  Google Scholar 

  • Okazaki MM, Nadler JV (1988) Protective effects of mossy fibre lesions against kainic acid induced seizures and neuronal degeneration. Neuroscience 26:763–781

    Article  CAS  PubMed  Google Scholar 

  • Okonkwo DO, Reece TB, Laurent JJ, Hawkins AS, Ellman PI, Linden J, Kron IL, Tribble CG, Stone JR, Kern JA (2006) A comparison of adenosine A(2A) agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits. J Neurosurg 4:64–70

    Google Scholar 

  • Oliveira JC, Constantino MD, Sebastiao AM, Ribeiro JA (1995) Ascorbate/Fe3 + -induced peroxidation and inhibition of the binding of A1 adenosine receptor ligands in rat-brain membranes. Neurochem Int 26:263–268

    Article  CAS  PubMed  Google Scholar 

  • Ongini E, Fredholm BB (1996) Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 17:364–372

    Article  CAS  PubMed  Google Scholar 

  • Ongini E, Adami M, Ferri C, Bertorelli R (1997) Adenosine A2A receptors and neuroprotection. Ann NY Acad Sci 825:30–48

    Article  CAS  PubMed  Google Scholar 

  • Ongini E, Monopoli A, Impagnatiello F, Fredduzzi S, Schwarzschild M, Chen JF (2001) Dual actions of A2A adenosine receptor antagonists on motor dysfunction and neurodegenerative processes. Drug Dev Res 52:379–386

    Article  CAS  Google Scholar 

  • Pagonopoulou O, Angelatou F (1992) Reduction of A1 adenosine receptors in cortex, hippocampus and cerebellum in ageing mouse brain. Neuroreport 3:735–737

    Article  CAS  PubMed  Google Scholar 

  • Palmer TM, Poucher SM, Jacobson KA, Stiles GL (1995) 125I-4-[7-amino-2-{2-furyl} {1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol, a high affinity antagonist radioligand selective for the A2A adenosine receptor. Mol Pharmacol 48:970–974

    CAS  PubMed  Google Scholar 

  • Parkinson FE, Rudolphi KA, Fredholm BB (1994) Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischaemia. Gen Pharmacol 25:1053–1058

    CAS  PubMed  Google Scholar 

  • Pazzagli M, Corsi C, Latini S, Pedata F, Pepeu G (1994) In vivo regulation of extracellular adenosine levels in the cerebral cortex by NMDA and muscarinic receptors. Eur J Pharmacol 254:277–282

    Article  CAS  PubMed  Google Scholar 

  • Pedata F, Corsi C, Melani A, Bordoni F, Latini S (2001) Adenosine extracellular brain concentrations and role of A2A receptors in ischemia. Ann N Y Acad Sci 939:74–84

    Article  CAS  PubMed  Google Scholar 

  • Pedata F, Gianfriddo M, Turchi D, Melani A (2005) The protective effect of adenosine A(2A) receptor antagonism in cerebral ischemia. Neurol Res 27:169–174

    Article  CAS  PubMed  Google Scholar 

  • Phillis JW (1995) The effects of selective A1 and A2A adenosine receptor antagonists on cerebral ischemic injury in the gerbil. Brain Res 705:79–84

    Article  CAS  PubMed  Google Scholar 

  • Phillis JW, O’Regan MH (1993) Prevention of ischemic brain injury by adenosine receptor activation. Drug Dev Res 28:390–394

    Article  CAS  Google Scholar 

  • Pierson PM, Peteri-Brunbäck B, Pisani DF, Abbracchio MP, Mienville JM, Rosso L (2007) A(2b) receptor mediates adenosine inhibition of taurine efflux from pituicytes. Biol Cell 99:445–454

    Article  CAS  PubMed  Google Scholar 

  • Pignataro G, Simon RP, Boison D (2007) Transgenic overexpression of adenosine kinase aggravates cell death in ischemia. J Cereb Blood Flow Metab 27:1–5

    Article  CAS  PubMed  Google Scholar 

  • Pintor A, Galluzzo M, Grieco R, Pèzzola A, Reggio R, Popoli P (2004) Adenosine A2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors. J Neurochem 89:152–156

    Article  CAS  PubMed  Google Scholar 

  • Pitsikas N, Borsini F (1997) The adenosine A1 receptor antagonist BIIP 20 counteracts scopolamine-induced behavioral deficits in the passive avoidance task in the rat. Eur J Pharmacol 328:19–22

    Article  CAS  PubMed  Google Scholar 

  • Poli A, Lucchi R, Vibio M, Barnabei O (1991) Adenosine and glutamate modulate each other’s release from rat hippocampal synaptosomes. J Neurochem 57:298–306

    Article  CAS  PubMed  Google Scholar 

  • Popoli P, Pèzzola A, Domenici MR, Sagratella S, Diana G, Caporali MG, Bronzetti E, Vega J, Scotti de Carolis A (1994) Behavioral and electrophysiological correlates of the quinolinic acid rat model of Huntington’s disease in rats. Brain Res Bull 35:329–335

    Article  CAS  PubMed  Google Scholar 

  • Popoli P, Betto P, Reggio R, Ricciarello G (1995) Adenosine A(2A) receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287:215–217

    Article  CAS  PubMed  Google Scholar 

  • Popoli P, Pintor A, Domenici MR, Frank C, Tebano MT, Pèzzola A, Scarchilli L, Quarta D, Reggio R, Malchiodi-Albedi F, Falchi M, Massotti M (2002) Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 22:1967–1975

    CAS  PubMed  Google Scholar 

  • Popoli P, Blum D, Martire A, Ledent C, Ceruti S, Abbracchio MP (2007) Functions, dysfunctions and possible therapeutic relevance of adenosine A2A receptors in Huntington’s disease. Prog Neurobiol 81:331–348

    Article  CAS  PubMed  Google Scholar 

  • Pousinha PA, Diogenes JM, Ribeiro AJ, Sebastiao AM (2006) Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine A2A receptors. Neurosci Lett 404:143–147

    Article  CAS  PubMed  Google Scholar 

  • Prediger RDS, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats: involvement of adenosine A(1) and A(2A) receptors. Neurobiol Ageing 26:957–964

    Article  CAS  Google Scholar 

  • Press NJ, Gessi S, Borea PA, Polosa R (2007) Therapeutic potential of adenosine receptor antagonists and agonists. Exp Opin Ther Pat 17:979–991

    Article  CAS  Google Scholar 

  • Prior C, Torres RJ, Puig JG (2006) Hypoxanthine effect on equilibrative and concentrative adenosine transport in human lymphocytes. Implications in the pathogenesis of Lesch–Nyhan syndrome. Nucleosides Nucleotides Nucl Acids 25:1065–1069

    Article  CAS  Google Scholar 

  • Pugliese AM, Latini S, Corradetti R, Pedata F (2003) Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. Br J Pharmacol 140:305–314

    Article  CAS  PubMed  Google Scholar 

  • Pugliese AM, Coppi E, Volpini R, Cristalli G, Corradetti R, Jeong LS, Jacobson KA, Pedata F (2007) Role of adenosine A(3) receptors on CA1 hippocampal transmission during oxygen-glucose deprivation episodes of different duration. Biochem Pharmacol 74:768–779

    Article  CAS  PubMed  Google Scholar 

  • Quintana JLB, Allam MF, Del Castillo AS, Navajas RFC (2007) Alzheimer’s disease and coffee: a review. Neurol Res 29:91–95

    Article  Google Scholar 

  • Ramakers BP, Riksen NP, Rongen GA, van der Hoeven JG, Smits P, Pickkers P (2006) The effect of adenosine receptor agonists on cytokine release by human mononuclear cells depends on the specific Toll-like receptor subtype used for stimulation. Cytokine 35:95–99

    Article  CAS  PubMed  Google Scholar 

  • Rathbone MP, Middlemiss PJ, Kim JK, Gysbers JW, Deforge SP, Smith RW, Hughes DW (1992) Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells. Neurosci Res 13:1–17

    Article  CAS  PubMed  Google Scholar 

  • Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MAR, Reed JK, Ciccarelli R, Di Iorio P, Caciagli F (1999) Trophic effects of purines in neurons and glial cells. Prog Neurobiol 59:663–690

    Article  CAS  PubMed  Google Scholar 

  • Reece TB, Okonkwo DO, Ellman PI, Warren PS, Smith RL, Hawkins AS, Linden J, Kron IL, Tribble CG, Kern JA (2004) The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A(2A) receptor activation. J Thorac Cardiovasc Surg 128:925–932

    CAS  PubMed  Google Scholar 

  • Reece TB, Kron IL, Okonkwo DO, Laurent JJ, Tache-Leon C, Maxey TS, Ellman PI, Linden J, Tribble CG, Kern JA (2006) Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism. J Vasc Surg 44:392–397

    Article  PubMed  Google Scholar 

  • Regenold JT, Illes P (1990) Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study. Naunyn–Schmied Arch Pharmacol 341:225–231

    CAS  Google Scholar 

  • Reggio R, Pezzola A, Popoli P (1999) The intrastratial injection of an adenosine A(2) receptor antagonist prevents frontal cortex EEG abnormalities in a rat model of Huntington’s disease. Brain Res 831:315–318

    Article  CAS  PubMed  Google Scholar 

  • Revan S, Montesinos MC, Naime D, Landau S, Cronstein BN (1996) Adenosine A2 receptor occupancy regulates stimulated neutrophil function via activation of a serine/threonine protein phosphatase. J Biol Chem 271:17114–17118

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro JA, Sebastiao AM, de Mendonça A (2002) Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 68:377–392

    Article  CAS  PubMed  Google Scholar 

  • Riedel W, Hogervorst E, Leboux R, Verhey F, Vanpraag H, Jolles J (1995) Caffeine attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 122:158–168

    Article  CAS  PubMed  Google Scholar 

  • Ritchie PK, Spangelo BL, Krzymowski DK, Rossiter TB, Kurth E, Judd AM (1997) Adenosine increases interleukin-6 release and decreases TNF release from rat adrenal zona glomerulosa cells, ovarian cells, anterior pituitary cells and peritoneal macrophages. Cytokine 9:187–198

    Article  CAS  PubMed  Google Scholar 

  • Rivkees SA, Price SL, Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localisation in the hippocampal formation, cerebral cortex, cerebellum and basal ganglia. Brain Res 677:193–203

    Article  CAS  PubMed  Google Scholar 

  • Rivkees SA, Thevananther S, Hao H (2000) Are A3 adenosine receptors expressed in the brain? Neuroreport 11:1025–1030

    Article  CAS  PubMed  Google Scholar 

  • Robledo P, Ursu G, Mahy N (1999) Effects of adenosine and gamma-aminobutyric acid A receptor antagonists on N-methyl-D-aspartate induced neurotoxicity in the rat hippocampus. Hippocampus 9:527–533

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez A, Martin M, Albasanz JL, Barrachina M, Espinosa JC, Torres JM, Ferrer I (2006) Adenosine A(1) receptor protein levels and activity is increased in the cerebral cortex in Creutzfeldt–Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP mice. J Neuropathol Exp Neurol 65:964–975

    Article  CAS  PubMed  Google Scholar 

  • Rosi S, McGann K, Hauss-Wegrzyniak B, Wenk GL (2003) The influence of brain inflammation upon neuronal adenosine A(2B) receptors. J Neurochem 86:220–227

    Article  CAS  PubMed  Google Scholar 

  • Rubaj A, Zgodzinski W, Sieklucka-Dziuba M (2003) The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment. Behav Brain Res 141:11–17

    Article  CAS  PubMed  Google Scholar 

  • Rudolphi KA, Schubert P (1997) Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav Brain Res 83:123–128

    Article  CAS  PubMed  Google Scholar 

  • Rudolphi KA, Keil M, Hinze HJ (1987) Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: a behavioural and histopathological study. J Cereb Blood Flow Metab 7:74–81

    CAS  PubMed  Google Scholar 

  • Rudolphi KA, Keil M, Fastbom J, Fredholm BB (1989) Ischemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment. Neurosci Lett 103:275–280

    Article  CAS  PubMed  Google Scholar 

  • Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB (1992) Adenosine and brain ischaemia. Cerebrovasc Brain Metab Rev 4:346–369

    CAS  PubMed  Google Scholar 

  • Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-α expression by adenosine: role of A3 adenosine receptors. J Immunol 156:3435–3442

    CAS  PubMed  Google Scholar 

  • Saura J, Angulo E, Ejarque A, Casado V, Tusell JM, Moratalla R, Chen JF, Schwarzschild MA, Lluis C, Franco R, Serratosa J (2005) Adenosine A(2A) receptor stimulation potentiates nitric oxide release by activated microglia. J Neurochem 95:919–929

    Article  CAS  PubMed  Google Scholar 

  • Scatena R, Martorana GE, Bottoni P, Botta G, Pastore P, Giardina B (2007) An update on pharmacological approaches to neurodegenerative diseases. Exp Opin Invest Drugs 16:59–72

    Article  CAS  Google Scholar 

  • Scattoni ML, Valanzano A, Pezzola A, De March Z, Fusco FR, Popoli P, Calamandrei G (2007) Adenosine A(2A) receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington’s disease. Behav Brain Res 176:216–221

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann SN, Jacobs O, Vanderhaegen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridisation histochemistry study. J Neurochem 57:1062–1067

    Article  CAS  PubMed  Google Scholar 

  • Schingnitz G, Kufnermuhl U, Ensinger H, Lehr E, Kuhn FJ (1991) Selective A1-antagonists for treatment of cognitive deficits. Nucleosides Nucleotides 10:1067–1076

    Article  CAS  Google Scholar 

  • Scholz KP, Miller RJ (1992) Inhibition of quantal transmitter release in the absence of calcium influx by a G protein-linked adenosine receptor at hippocampal synapses. Neuron 8:1139–1150

    Article  CAS  PubMed  Google Scholar 

  • Schubert P, Ferroni S, Mager R (1991) Pharmacological blockade of chloride pumps on chloride channels reduces the adenosine-mediated depression of stimulus train-evoked calcium fluxes in rat hippocampal slices. Neurosci Lett 124:174–177

    Article  CAS  PubMed  Google Scholar 

  • Schubert P, Ogata T, Ferroni S, McRae A, Nakamura Y, Rudolphi K (1996) Modulation of glial cell signaling by adenosine and pharmacological reinforcement: a neuroprotective strategy? Mol Chem Neuropathol 28:185–190

    Article  CAS  PubMed  Google Scholar 

  • Schubert P, Ogata T, Rudolphi K, Marchini C, McRae A, Ferroni S (1997) Support of homeostatic glial cell signaling: a novel therapeutic approach by propentofylline. Ann NY Acad Sci 826:337–347

    Article  CAS  PubMed  Google Scholar 

  • Schurr A, Reid KH, Tseng MT, West C, Rigor BM (1986) Adaptation of adult brain-tissue to anoxia and hypoxia invitro. Brain Res 374:244–248

    Article  CAS  PubMed  Google Scholar 

  • Sebastiao AM, Ribeiro JA (1992) Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus. Neurosci Lett 138:41–44

    Article  CAS  PubMed  Google Scholar 

  • Sebastiao AM, Ribeiro JA (1996) Adenosine A(2) receptor-mediated excitatory actions on the nervous system. Progr Neurobiol 48:167–189

    Article  CAS  Google Scholar 

  • Sei Y, von Lubitz DKJE, Abbracchio MP, Ji X-D, Jacobson KA (1997) Adenosine A3 receptor agonist-induced neurotoxicity in rat cerebellar granule neurons. Drug Dev Res 40:267–273

    Article  CAS  Google Scholar 

  • Selley ML (2004) Increased homocysteine and decreased adenosine formation in Alzheimer’s disease. Neurol Res 26:554–557

    Article  CAS  PubMed  Google Scholar 

  • Sheardown MJ, Knutsen LJS (1996) Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS21680. Drug Dev Res 39:108–114

    Article  CAS  Google Scholar 

  • Shen H, Zhang L, Yuen D, Logan R, Jung BP, Zhang G, Eubanks JH (2002) Expression and function of A1 adenosine receptors in the rat hippocampus following transient forebrain ischemia. Neuroscience 114:547–556

    Article  CAS  PubMed  Google Scholar 

  • Simpson RE, O’Regan MH, Perkins LM, Phillis JW (1992) Excitatory transmitter amino acid release from the ischaemic rat cerebral cortex: effects of adenosine recptor agonists and antagonists. J Neurochem 58:1683–1690

    Article  CAS  PubMed  Google Scholar 

  • Sperk G (1994) Kainic acid seizures in the rat. Prog Neurobiol 42:1–32

    Article  CAS  PubMed  Google Scholar 

  • Spignoli G, Pedata F, Pepeu G (1984) A1 and A2 adenosine receptors modulate acetylcholine release from brain slices. Eur J Pharmacol 97:341–342

    Article  CAS  PubMed  Google Scholar 

  • Stone TW (1993) The neuropharmacology of quinolinic acid and kynurenic acid. Pharmacol Rev 45:309–379

    CAS  PubMed  Google Scholar 

  • Stone TW (2001) Kynurenines in the CNS: from endogenous obscurity to clinical relevance. Prog Neurobiol 64:185–218

    Article  CAS  PubMed  Google Scholar 

  • Stone TW, Darlington LG (2002) Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov 1:609–620

    Article  CAS  PubMed  Google Scholar 

  • Stone TW, Perkins MN (1981) Quinolinic acid: a potent endogenous excitant at amino acid receptors in the CNS. Eur J Pharmacol 72:411–412

    Article  CAS  PubMed  Google Scholar 

  • Sutherland GR, Peeling J, Lesiuk HJ, Brownstone RM, Rydzy M, Saunders JK, Geiger JD (1991) The effects of caffeine on ischemic neuronal injury as determined by magnetic-resonance-imaging and histopathology. Neuroscience 42:171–182

    Article  Google Scholar 

  • Suzuki F, Shimada J, Shiozaki S, Ichikawa S, Ishii A, Nakamura J, Nonaka H, Kobayashi H, Fuse E (1993) Adenosine A1 antagonists. 3. Structure–activity relationships on amelioration against scopolamine- or N 6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance. J Med Chem 36:2508–2518

    Article  CAS  PubMed  Google Scholar 

  • Svenningsson P, Hall H, Sedvall G, Fredholm BB (1997) Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study. Synapse 27:322–335

    Article  CAS  PubMed  Google Scholar 

  • Szot P, Sanders RC, Murray TF (1987) Theophylline-induced up-regulation of adenosine-A1-receptors associated with reduced sensitivity to convulsants. Neuropharmacology 26: 1173–1180

    Article  CAS  PubMed  Google Scholar 

  • Tarditi A, Camurri A, Varani K, Borea PA, Woodman B, Bates G, Cattaneo E, Abbracchio MP (2006) Early and transient alteration of adenosine A(2A) receptor signaling in a mouse model of Huntington disease. Neurobiol Dis 23:44–53

    Article  CAS  PubMed  Google Scholar 

  • Tebano MT, Pintor A, Frank C, Domenici MR, Martire A, Pepponi R, Potenza RL, Grieco R, Popoli P (2004) Adenosine A(2A) receptor blockade differentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum. J Neurosci Res 77:100–107

    Article  CAS  PubMed  Google Scholar 

  • Torres RJ, DeAntonio I, Prior C, Puig JG (2004) Effects of hypoxanthine on adenosine transport in human lymphocytes. Implications in the pathogenesis of Lesch–Nyhan syndrome. Nucleosides Nucleotides Nucl Acids 23:1177–1179

    Article  CAS  Google Scholar 

  • Traversa U, Rosati AM, Chiara F, Rodolfo V (1994) Effects of chronic administration of adenosine antagonists on adenosine A1 and A2A receptors in mouse brain. In vivo 8:1073–1078

    CAS  PubMed  Google Scholar 

  • Trincavelli ML, Marroni M, Tuscano D, Ceruti S, Mazzola A, Mitro N, Abbracchio MP, Martini C (2004) Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in human astroglial cells. J Neurochem 91:1180–1190

    Article  CAS  PubMed  Google Scholar 

  • Trincavelli ML, Tonazzini I, Montali M, Abbracchio MP, Martini C (2008) Short-term TNF-α treatment induced A2B adenosine receptor desensitization in human astroglial cells. J Cell Biochem 104:150–161

    Article  CAS  PubMed  Google Scholar 

  • Trussel LD, Jackson MB (1985) Adenosine activated potassium conductance in cultured striatal neurones. Proc Nat Acad Sci USA 82:4857–4861

    Article  Google Scholar 

  • Tsutsui S, Schnermann J, Noorbakhsh F, Henry S, Yong VW, Winston BW, Warren K, Power C (2004) A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 24:1521–1529

    Article  CAS  PubMed  Google Scholar 

  • Ulas J, Brunner LC, Nguyen L, Cotman CW (1993) Reduced density of adenosine-A1-receptors and preserved coupling of adenosine-A1-receptors to G-proteins in Alzheimer hippocampus: a quantitative autoradiographic study. Neuroscience 52:843–854

    Article  CAS  PubMed  Google Scholar 

  • Van der Schyf CJ, Gal S, Geldenhuys WJ, Youdim MBH (2006) Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases. Expert Opin Invest Drugs 15:873- 886

    Article  CAS  Google Scholar 

  • van Gelder BM, Buijsse B, Tijhuis M, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D (2007) Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr 61:226–232

    Article  PubMed  Google Scholar 

  • Varani K, Gessi S, Dionisotti S, Ongini E, Borea PA (1998) [3H]-SCH58261 labelling of functional A2A receptors in human neutrophil membranes. Br J Pharmacol 123:1723–1731

    Article  CAS  PubMed  Google Scholar 

  • Varani K, Rigamonti D, Sipione S, Camurri A, Borea PA, Cattabeni F, Abbracchio MP, Cattaneo E (2001) Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin. FASEB J 15:1245–1247

    CAS  PubMed  Google Scholar 

  • Varani K, Abbracchio MP, Cannella M, Cislaghi G, Giallonardo P, Mariotti C, Cattabriga E, Cattabeni F, Borea PA, Squitieri F, Cattaneo E (2003) Aberrant A2A receptor function in peripheral blood cells in Huntington’s disease. FASEB J 17:2148–2150

    CAS  PubMed  Google Scholar 

  • Varani K, Bachoud-Lévi AC, Mariotti C, Tarditi A, Abbracchio MP, Gasperi V, Borea PA, Dolbeau G, Gellera C, Solari A, Rosser A, Naji J, Handley O, Maccarrone M, Peschanski M, DiDonato S, Cattaneo E (2007) Biological abnormalities of peripheral A(2A) receptors in a large representation of polyglutamine disorders and Huntington’s disease stages. Neurobiol Dis 27:36–43

    Article  CAS  PubMed  Google Scholar 

  • Virgili M, Poli A, Contestabile A, Migani P, Barnabei O (1986) Synaptosomal release of newly synthesised or recently accumulated amino acids; differential effects of kainic acid on naturally occurring excitatory amino acids and on [D-3H]-aspartate. Neurochem Int 9:29–33

    Article  CAS  PubMed  Google Scholar 

  • Virus RM, Baglajewski T, Radulovacki M (1984) [3H]N 6-(L-Phenylisopropyl) adenosine binding in brains from young and old rats. Neurobiol Aging 5:61–62

    Article  CAS  PubMed  Google Scholar 

  • von Lubitz DKEJ, Dambrosia JM, Redmond DJ (1989) Protective effect of cyclohexyladenosine in treatment of cerebral ischaemia in gerbils. Neuroscience 30:451–462

    Article  Google Scholar 

  • von Lubitz DK, Paul IA, Bartus RT, Jacobson KA (1993) Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory. Eur J Pharmacol 249:271–280

    Article  Google Scholar 

  • von Lubitz DK, Lin RC, Melman N, Ji XD, Carter MF, Jacobson KA (1994a) Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischaemia. Eur J Pharmacol 256:161–167

    Article  Google Scholar 

  • von Lubitz DK, Lin RC, Popik P, Carter MF, Jacobson KA (1994b) Adenosine A3 receptor stimulation and cerebral ischaemia. Eur J Pharmacol 263:59–67

    Article  Google Scholar 

  • von Lubitz DKJE, Kim J, Beenhakker M, Carter MF, Lin RCS, Meshulam Y, Daly JW, Shi D, Zhou LM, Jacobson KA (1995a) Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A(1) receptors. Eur J Pharmacol 283:185–192

    Article  Google Scholar 

  • von Lubitz DKJE, Lin RC-S, Jacobson KA (1995b) Cerebral ischaemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295–302

    Article  Google Scholar 

  • von Lubitz DK, Lin RC, Paul IA, Beenhakker M, Boyd M, Bischofberger N, Jacobson KA (1996) Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. Eur J Pharmacol 316:171–179

    Article  Google Scholar 

  • von Lubitz DJKE, Lin RCS, Bischofberger N, Beenhakker M, Boyd M, Lipartowska R, Jacobson KA (1999a) Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist. Eur J Pharmacol 369:313–317

    Article  Google Scholar 

  • von Lubitz DKJE, Lin RC-S, Boyd M, Bischofberger N, Jacobson KA (1999b) Chronic administration of adenosine A3 receptor agonist and cerebral ischaemia: neuronal and glial effects. Eur J Pharmacol 367:157–163

    Article  Google Scholar 

  • Von Lubitz DKJE, Simpson KL, Lin RCS (2001) Right thing at a wrong time? Adenosine A(3) receptors and cerebroprotection in stroke. Neuroprotective Agents 939:85–96

    Google Scholar 

  • Wagner DR, Combes A, McTiernan C, Sanders VJ, Lemster B, Feldman AM (1998a) Adenosine inhibits lipopolysaccharide-induced cardiac expression of TNFα. Circ Res 82:47–56

    CAS  PubMed  Google Scholar 

  • Wagner DR, McTiernan C, Sanders VJ, Feldman AM (1998b) Adenosine inhibits lipopolysaccharide-induced secretion of TNF-α in the failing human heart. Circulation 97:521–524

    CAS  PubMed  Google Scholar 

  • Warskulat U, Heller-Stilb B, Oermann E, Zilles K, Haas H, Lang F, Häussinger D (2007) Phenotype of the taurine transporter knockout mouse. Methods Enzymol 428:439–58

    Article  CAS  PubMed  Google Scholar 

  • Wirkner K, Assmann H, Koles l, Gerevich Z, Franke H, Norenberg, Boehm R, Illes P (2000) Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. Br J Pharmacol 130:259–269

    Article  CAS  PubMed  Google Scholar 

  • Wirkner K, Gerevich Z, Krause T, Gunther A, Koles L, Schneider D, Norenberg W, Illes P (2004) Adenosine A(2A) receptor-induced inhibition of NMDA and GABA(A) receptor-mediated synaptic currents in a subpopulation of rat striatal neurons. Neuropharmacology 46:994–1007

    Article  CAS  PubMed  Google Scholar 

  • Wu LG, Saggau P (1997) Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 20:204–212

    Article  CAS  PubMed  Google Scholar 

  • Yamada K, Tanaka T, Senzaki K, Kameyama T, Nabeshima T (1998) Propentofylline improves learning and memory deficits in rats induced by β-amyloid protein-(1–40). Eur J Pharmacol 349:15–22

    Article  CAS  PubMed  Google Scholar 

  • Yao ZH, Gross GJ (1994) The ATP-dependent potassium channel - an endogenous cardioprotective mechanism. J Cardiovasc Pharmacol 24: S28–S34

    Article  CAS  PubMed  Google Scholar 

  • Yao Y, Sei Y, Abbracchio MP, Jiang JL, Kim YC, Jacobson KA (1997) Adenosine A3 receptor agonists protect HL-60 and U-937 cells from apoptosis induced by A3 antagonists. Biochem Biophys Res Commun 232:317–22

    Article  CAS  PubMed  Google Scholar 

  • Yoshida M, Nakakimura K, Cui YJ, Matsumoto M, Sakabe T (2004) Adenosine a, receptor antagonist and mitochondrial ATP-sensitive potassium channel blocker attenuate the tolerance to focal cerebral ischemia in rats. J Cereb Blood Flow Metab 24:771–779

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka K, Saitoh O, and Nakata H (2001) Heteromeric association creates a P2Y-like adenosine receptor. Proc Natl Acad Sci USA 98:7617–7622

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka K, Hosada R, Kuroda Y, Nakata H (2002a) Hetero-oligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains. FEBS Lett 531:299–303

    Article  CAS  PubMed  Google Scholar 

  • Yoshioka K, Saitoh O, Nakata H (2002b) Agonist-promoted heteromeric oligomerization between adenosine A1 and P2Y1 receptors in living cells. FEBS Lett 523:147–151

    Article  CAS  PubMed  Google Scholar 

  • Yu LQ, Huang Z, Mariani J, Wang Y, Moskowitz M, Chen JF (2004) Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat Med 10:1081–1087

    Article  CAS  PubMed  Google Scholar 

  • Zarrindast MR, Shafaghi B (1994) Effects of adenosine receptor agonists and antagonists on acquisition of passive avoidance learning. Eur J Pharmacol 256:233–239

    Article  CAS  PubMed  Google Scholar 

  • Zhao ZQ, McGee S, Nakanishi K, Toombs CF, Johnston WE, Ashar MS, Vinten-Johansen J (1993) Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit. Circulation 88:709–719

    CAS  PubMed  Google Scholar 

  • Zhou AM, Li WB, Li QJ, Liu HQ, Feng RF, Zhao HG (2004) A short cerebral ischemic preconditioning up-regulates adenosine receptors in the hippocampal CA1 region of rats. Neurosci Res 48:397–404

    Article  CAS  PubMed  Google Scholar 

  • Zhou QY, Li C, Olah ME, Johnson RA, Stiles GL, Civelli O (1992) Molecular cloning and characterisation of an adenosine receptor: the A3 receptor. Proc Nat Acad Sci USA 89:7432–7436

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

    Trevor W. Stone

  2. Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological Sciences, University of Milan, via Balzaretti, 9, Milan, Italy

    Stefania Ceruti & Mariapia P. Abbracchio

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  1. Trevor W. Stone
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  2. Stefania Ceruti
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  3. Mariapia P. Abbracchio
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Correspondence to Trevor W. Stone .

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  1. Endacea, Inc.,, Davis Drive 2, Research Triangle Park, 27709-2076, U.S.A.

    Constance N. Wilson

  2. Health Sciences Center, West Virginia University, Health Sciences S. 2267, Morgantown, 26506-9104, U.S.A.

    S. Jamal Mustafa

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Stone, T.W., Ceruti, S., Abbracchio, M.P. (2009). Adenosine Receptors and Neurological Disease: Neuroprotection and Neurodegeneration. In: Wilson, C., Mustafa, S. (eds) Adenosine Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89615-9_17

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