QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (155) Citing Articles via Google Scholar Google Scholar Articles by Dunwiddie, T. V. Articles by Proctor, W. R. Search for Related Content PubMed PubMed Citation Articles by Dunwiddie, T. V. Articles by Proctor, W. R.

 Previous Article  |  Next Article 

Volume 17, Number 20, Issue of October 15, 1997 pp. 7673-7682
Copyright ©1997 Society for Neuroscience

Adenine Nucleotides Undergo Rapid, Quantitative Conversion to Adenosine in the Extracellular Space in Rat Hippocampus

Received June 5, 1997; revised August 4, 1997; accepted August 5, 1997.

Thomas V. Dunwiddie^{1, 2}, Lihong Diao¹, and William R. Proctor^{1, 2}

¹ Program in Neuroscience and Department of Pharmacology, University of Colorado Health Science Center, Denver, Colorado 80262, and ² Veterans Administration Medical Research Service, Denver, Colorado 80220

There are multiple mechanisms by which adenine nucleotides can be released into the extracellular space in brain. Adenine nucleotides are converted extracellularly to adenosine, which then acts on adenosine receptors to elicit physiological responses, but the rate at which this conversion takes place is unknown. In the present experiments, adenine nucleotides were applied to individual hippocampal neurons, and the subsequent activation of a postsynaptic K⁺ conductance by adenosine A₁ receptors was used to determine the rate of adenosine formation. None of the adenine nucleotides tested (cAMP, AMP, ADP, and ATP) activated A₁ receptors directly at the concentrations tested (200 µM). AMP, ADP, and ATP were all rapidly converted to adenosine, with a T_1/2 for ATP conversion to adenosine of ~200 msec, and the last step in this pathway (transformation of AMP to adenosine by 5-nucleotidase) seems to be the rate-limiting step. As we have reported previously, cAMP is converted to adenosine as well, but on a much slower time scale than any of the other nucleotides tested. These experiments demonstrate that fast, localized release of AMP, ADP, or ATP can result in a transient activation of adenosine receptors but that this is unlikely to occur with cAMP. The existence of a highly active ecto-nucleotidase pathway in brain provides a mechanism for the rapid generation of adenosine after the release of adenine nucleotides into the extracellular space.

Key words: adenosine; adenine nucleotides; adenosine receptors; hippocampus; electrophysiology; 5-nucleotidase; P₁ receptors

This article has been cited by other articles:

				K. Kirmse, A. Dvorzhak, R. Grantyn, and S. Kirischuk Developmental Downregulation of Excitatory GABAergic Transmission in Neocortical Layer I via Presynaptic Adenosine A1 Receptors Cereb Cortex, February 1, 2008; 18(2): 424 - 432. [Abstract] [Full Text] [PDF]

				J. H.-C. Lin, N. Lou, N. Kang, T. Takano, F. Hu, X. Han, Q. Xu, D. Lovatt, A. Torres, K. Willecke, et al. A Central Role of Connexin 43 in Hypoxic Preconditioning J. Neurosci., January 16, 2008; 28(3): 681 - 695. [Abstract] [Full Text] [PDF]

				A. E. Fink, J. Sarinana, E. E. Gray, and T. J. O'Dell Activity-Dependent Depression of Local Excitatory Connections in the CA1 Region of Mouse Hippocampus J Neurophysiol, June 1, 2007; 97(6): 3926 - 3936. [Abstract] [Full Text] [PDF]

				M. J. Wall and N. Dale Auto-inhibition of rat parallel fibre-Purkinje cell synapses by activity-dependent adenosine release J. Physiol., June 1, 2007; 581(2): 553 - 565. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				A. R. Lorier, A. G. Huxtable, D. M. Robinson, J. Lipski, G. D. Housley, and G. D. Funk P2Y1 Receptor Modulation of the Pre-Botzinger Complex Inspiratory Rhythm Generating Network In Vitro J. Neurosci., January 31, 2007; 27(5): 993 - 1005. [Abstract] [Full Text] [PDF]

				J. Mojsilovic-Petrovic, G.-B. Jeong, A. Crocker, A. Arneja, S. David, D. Russell, and R. G. Kalb Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors J. Neurosci., September 6, 2006; 26(36): 9250 - 9263. [Abstract] [Full Text] [PDF]

				A. K. Filippov, R. C. Y. Choi, J. Simon, E. A. Barnard, and D. A. Brown Activation of P2Y1 Nucleotide Receptors Induces Inhibition of the M-Type K+ Current in Rat Hippocampal Pyramidal Neurons J. Neurosci., September 6, 2006; 26(36): 9340 - 9348. [Abstract] [Full Text] [PDF]

				T. A. Ponzio, Y.-F. Wang, and G. I. Hatton Activation of adenosine A2A receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R359 - R366. [Abstract] [Full Text] [PDF]

				P. G. Haydon and G. Carmignoto Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev, July 1, 2006; 86(3): 1009 - 1031. [Abstract] [Full Text] [PDF]

				T. Fellin, O. Pascual, and P. G. Haydon Astrocytes Coordinate Synaptic Networks: Balanced Excitation and Inhibition Physiology, June 1, 2006; 21(3): 208 - 215. [Abstract] [Full Text] [PDF]

				A. Y. C. Wong, B. Billups, J. Johnston, R. J. Evans, and I. D. Forsythe Endogenous Activation of Adenosine A1 Receptors, but Not P2X Receptors, During High-Frequency Synaptic Transmission at the Calyx of Held J Neurophysiol, June 1, 2006; 95(6): 3336 - 3342. [Abstract] [Full Text] [PDF]

				O. Pascual, K. B. Casper, C. Kubera, J. Zhang, R. Revilla-Sanchez, J.-Y. Sul, H. Takano, S. J. Moss, K. McCarthy, and P. G. Haydon Astrocytic Purinergic Signaling Coordinates Synaptic Networks Science, October 7, 2005; 310(5745): 113 - 116. [Abstract] [Full Text] [PDF]

				V. F. Safiulina, A. M. Kasyanov, R. Giniatullin, and E. Cherubini Adenosine Down-Regulates Giant Depolarizing Potentials in the Developing Rat Hippocampus by Exerting a Negative Control on Glutamatergic Inputs J Neurophysiol, October 1, 2005; 94(4): 2797 - 2804. [Abstract] [Full Text] [PDF]

				R. J. Rodrigues, T. Almeida, P. J. Richardson, C. R. Oliveira, and R. A. Cunha Dual Presynaptic Control by ATP of Glutamate Release via Facilitatory P2X1, P2X2/3, and P2X3 and Inhibitory P2Y1, P2Y2, and/or P2Y4 Receptors in the Rat Hippocampus J. Neurosci., July 6, 2005; 25(27): 6286 - 6295. [Abstract] [Full Text] [PDF]

				V. F Safiulina, A. M Kasyanov, E. Sokolova, E. Cherubini, and R. Giniatullin ATP contributes to the generation of network-driven giant depolarizing potentials in the neonatal rat hippocampus J. Physiol., June 15, 2005; 565(3): 981 - 992. [Abstract] [Full Text] [PDF]

				T. A. Ponzio and G. I. Hatton Adenosine Postsynaptically Modulates Supraoptic Neuronal Excitability J Neurophysiol, January 1, 2005; 93(1): 535 - 547. [Abstract] [Full Text] [PDF]

				M. Kawamura, C. Gachet, K. Inoue, and F. Kato Direct Excitation of Inhibitory Interneurons by Extracellular ATP Mediated by P2Y1 Receptors in the Hippocampal Slice J. Neurosci., December 1, 2004; 24(48): 10835 - 10845. [Abstract] [Full Text] [PDF]

				M. Kukley, P. Stausberg, G. Adelmann, I. P. Chessell, and D. Dietrich Ecto-Nucleotidases and Nucleoside Transporters Mediate Activation of Adenosine Receptors on Hippocampal Mossy Fibers by P2X7 Receptor Agonist 2'-3'-O-(4-Benzoylbenzoyl)-ATP J. Neurosci., August 11, 2004; 24(32): 7128 - 7139. [Abstract] [Full Text] [PDF]

				S. L. Stella Jr., E. J. Bryson, L. Cadetti, and W. B. Thoreson Endogenous Adenosine Reduces Glutamatergic Output From Rods Through Activation of A2-Like Adenosine Receptors J Neurophysiol, July 1, 2003; 90(1): 165 - 174. [Abstract] [Full Text] [PDF]

				S. Ortinau, B. Laube, and H. Zimmermann ATP Inhibits NMDA Receptors after Heterologous Expression and in Cultured Hippocampal Neurons and Attenuates NMDA-Mediated Neurotoxicity J. Neurosci., June 15, 2003; 23(12): 4996 - 5003. [Abstract] [Full Text] [PDF]

				E. Panther, S. Corinti, M. Idzko, Y. Herouy, M. Napp, A. la Sala, G. Girolomoni, and J. Norgauer Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells Blood, May 15, 2003; 101(10): 3985 - 3990. [Abstract] [Full Text] [PDF]

				E. A. Newman Glial Cell Inhibition of Neurons by Release of ATP J. Neurosci., March 1, 2003; 23(5): 1659 - 1666. [Abstract] [Full Text] [PDF]

				D. H. Brager and S. M. Thompson Activity-Dependent Release of Adenosine Contributes to Short-Term Depression at CA3-CA1 Synapses in Rat Hippocampus J Neurophysiol, January 1, 2003; 89(1): 22 - 26. [Abstract] [Full Text] [PDF]

				S. A. Masino, L. Diao, P. Illes, N. R. Zahniser, G. A. Larson, B. Johansson, B. B. Fredholm, and T. V. Dunwiddie Modulation of Hippocampal Glutamatergic Transmission by ATP Is Dependent on Adenosine A1 Receptors J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 356 - 363. [Abstract] [Full Text] [PDF]

				B. U. Failer, N. Braun, and H. Zimmermann Cloning, Expression, and Functional Characterization of a Ca2+-dependent Endoplasmic Reticulum Nucleoside Diphosphatase J. Biol. Chem., September 27, 2002; 277(40): 36978 - 36986. [Abstract] [Full Text] [PDF]

				K. M. Gerstin, M. J. Dresser, and K. M. Giacomini Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT Am J Physiol Renal Physiol, August 1, 2002; 283(2): F344 - F349. [Abstract] [Full Text] [PDF]

				J. N. Armstrong, T. B. Brust, R. G. Lewis, and B. A. MacVicar Activation of Presynaptic P2X7-Like Receptors Depresses Mossy Fiber-CA3 Synaptic Transmission through p38 Mitogen-Activated Protein Kinase J. Neurosci., July 15, 2002; 22(14): 5938 - 5945. [Abstract] [Full Text] [PDF]

				N. A. Farahbakhsh and M. C. Cilluffo P2 Purinergic Receptor-Coupled Signaling in the Rabbit Ciliary Body Epithelium Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2317 - 2325. [Abstract] [Full Text] [PDF]

				I. Matsuoka, S. Ohkubo, J. Kimura, and Y. Uezono Adenine Nucleotide-Induced Activation of Adenosine A2B Receptors Expressed in Xenopus laevis Oocytes: Involvement of a Rapid and Localized Adenosine Formation by Ectonucleotidases Mol. Pharmacol., March 1, 2002; 61(3): 606 - 613. [Abstract] [Full Text] [PDF]

				J. H. Lee, T. Chiba, and D. C. Marcus P2X2 Receptor Mediates Stimulation of Parasensory Cation Absorption by Cochlear Outer Sulcus Cells and Vestibular Transitional Cells J. Neurosci., December 1, 2001; 21(23): 9168 - 9174. [Abstract] [Full Text] [PDF]

				B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, K.-N. Klotz, and J. Linden International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors Pharmacol. Rev., December 1, 2001; 53(4): 527 - 552. [Abstract] [Full Text] [PDF]

				B. S. Khakh, G. Burnstock, C. Kennedy, B. F. King, R. A. North, P. Seguela, M. Voigt, and P. P. A. Humphrey International Union of Pharmacology. XXIV. Current Status of the Nomenclature and Properties of P2X Receptors and Their Subunits Pharmacol. Rev., March 1, 2001; 53(1): 107 - 118. [Abstract] [Full Text] [PDF]

				J. T. Williams, M. J. Christie, and O. Manzoni Cellular and Synaptic Adaptations Mediating Opioid Dependence Physiol Rev, January 1, 2001; 81(1): 299 - 343. [Abstract] [Full Text] [PDF]

				V. Mendoza-Fernández, R. D. Andrew, and C. Barajas-López ATP Inhibits Glutamate Synaptic Release by Acting at P2Y Receptors in Pyramidal Neurons of Hippocampal Slices J. Pharmacol. Exp. Ther., April 1, 2000; 293(1): 172 - 179. [Abstract] [Full Text]

				J. C. Rekling, G. D. Funk, D. A. Bayliss, X.-W. Dong, and J. L. Feldman Synaptic Control of Motoneuronal Excitability Physiol Rev, April 1, 2000; 80(2): 767 - 852. [Abstract] [Full Text] [PDF]

				B. S. Khakh, W. R. Proctor, T. V. Dunwiddie, C. Labarca, and H. A. Lester Allosteric Control of Gating and Kinetics at P2X4 Receptor Channels J. Neurosci., September 1, 1999; 19(17): 7289 - 7299. [Abstract] [Full Text] [PDF]

				S. J. Hong and C. C. Chang Evaluation of Intrinsic Modulation of Synaptic Transmission by ATP in Mouse Fast Twitch Muscle J Neurophysiol, November 1, 1998; 80(5): 2550 - 2558. [Abstract] [Full Text] [PDF]

				O. Manzoni, D. Pujalte, J. Williams, and J. Bockaert Decreased Presynaptic Sensitivity to Adenosine after Cocaine Withdrawal J. Neurosci., October 1, 1998; 18(19): 7996 - 8002. [Abstract] [Full Text] [PDF]

				N. Braun, Y. Zhu, J. Krieglstein, C. Culmsee, and H. Zimmermann Upregulation of the Enzyme Chain Hydrolyzing Extracellular ATP after Transient Forebrain Ischemia in the Rat J. Neurosci., July 1, 1998; 18(13): 4891 - 4900. [Abstract] [Full Text] [PDF]

				G. B. Miles, M. A. Parkis, J. Lipski, and G. D. Funk Modulation of phrenic motoneuron excitability by ATP: consequences for respiratory-related output in vitro J Appl Physiol, May 1, 2002; 92(5): 1899 - 1910. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help