Abstract
The Transient Receptor Potential Ankyrin 1 channel (TRPA1), is a member of the large TRP family of ion channels, and functions as a Ca2+ permeable non-selective cation channel in many different cell processes, ranging from sensory to homeostatic tasks. TRPA1 is highly conserved across the animal kingdom. The only mammalian TRPA subfamily member, TRPA1, is widely expressed in neuronal (e.g. sensory dorsal root and trigeminal ganglia neurons)- and in non-neuronal cells (e.g. epithelial cells, hair cells). It exhibits 14–19 amino-(N-)terminal ankyrin repeats, an unusual structural feature. The TRPA1 channel is activated by noxious cold (<17 °C) as well as by a plethora of chemical compounds that includes not only electrophilic compounds and oxidants that can modify, in an alkylative or oxidative fashion, nucleophilic cysteine residues in the channel’s N-terminus, but also compounds that do not covalently bind to the channel proteins (e.g. menthol, nifedipin). Based on localization and functional properties, TRPA1 is considered a key player in acute and chronic (neuropathic) pain and inflammation. Moreover, its role in the (patho)physiology of nearly all organ systems is anticipated, and will be discussed along with the potential of TRPA1 as a drug target for the management of various pathological conditions.
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References
Alenmyr L, Herrmann A, Hogestatt ED, Greiff L, Zygmunt PM (2011) TRPV1 and TRPA1 stimulation induces MUC5B secretion in the human nasal airway in vivo. Clin Physiol Funct Imaging 31:435–444
Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi JL, Sterner O, Bevan S, Hogestatt ED, Zygmunt PM (2011) TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol. Nat Commun 2:551
Andersson DA, Gentry C, Moss S, Bevan S (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci 28:2485–2494
Andersson DA, Gentry C, Moss S, Bevan S (2009) Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+. Proc Natl Acad Sci (USA) 106:8374–8379
Andersson KE, Gratzke C, Hedlund P (2010) The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int 106:1114–1127
Andrade EL, Ferreira J, Andre E, Calixto JB (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114
Andrade EL, Forner S, Bento AF, Leite DF, Dias MA, Leal PC, Koepp J, Calixto JB (2011) Trpa1 Receptor Modulation Attenuates Bladder Overactivity Induced by Spinal Cord Injury. Am J Physiol Ren Physiol 300:F1223–F1234
Andrade EL, Meotti FC, Calixto JB (2012) TRPA1 antagonists as potential analgesic drugs. Pharmacol Ther 133:189–204
Andre E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P (2009) Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol 158:1621–1628
Anke H, Sterner O (1991) Comparison of the antimicrobial and cytotoxic activities of twenty unsaturated sesquiterpene dialdehydes from plants and mushrooms. Planta Medica 57:344–346
Artim DE, Bazely F, Daugherty SL, Sculptoreanu A, Koronowski KB, Schopfer FJ, Woodcock SR, Freeman BA, de Groat WC (2011) Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder. Exp Neurol 232:90–99
Atoyan R, Shander D, Botchkareva NV (2009) Non-Neuronal Expression of Transient Receptor Potential Type A1 (TRPA1) in Human Skin. J Invest Dermatol 129:2312–2315
Aubdool AA, Brain SD (2011) Neurovascular aspects of skin neurogenic inflammation. J Investig Dermatol Symp Proc 15:33–39
Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857
Bang S, Hwang SW (2009) Polymodal Ligand Sensitivity of TRPA1 and Its Modes of Interactions. J Gen Physiol 133:257–262
Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci 26:2516–2523
Bang S, Yoo S, Yang TJ, Cho H, Kim YG, Hwang SW (2010) Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol 161:707–720
Banke TG (2011) The dilated TRPA1 channel pore state is blocked by amiloride and analogues. Brain Res 1381:21–30
Banke T, Chaplan S, Wickenden AD (2010) Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation. Am J Physiol Cell Physiol Cell Physiology 298:C1438–C1444
Baraldi PG, Preti D, Materazzi S, Geppetti P (2010) Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents. J Med Chem 53:5085–5107
Baraldi PG, Romagnoli R, Saponaro G, Aghazadeh Tabrizi M, Baraldi S, Pedretti P, Fusi C, Nassini R, Materazzi S, Geppetti P, Preti D (2012) 7-Substituted-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: A promising approach for treating pain and inflammation. Bioorg Med Chem 20:1690–1698
Bassoli A, Borgonovo G, Caimi S, Scaglioni L, Morini G, Moriello AS, Marzo VD, Petrocellis LD (2009) Taste-guided identification of high potency TRPA1 agonists from Perilla frutescens. Bioorg Med Chem 17:1636–1639
Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 Mediates the Inflammatory Actions of Environmental Irritants and Proalgesic Agents. Cell 124:1269–1282
Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, Julius D, Jordt SE, Zygmunt PM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A 102:12248–12252
Bautista DM, Sigal YM, MilsteinA D, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D (2008) Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels. Nat Neurosci 11:772–779
Belvisi MG, Dubuis E, Birrell MA (2011) Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest 140:1040–1047
Benedikt J, Samad A, Ettrich R, Teisinger J, Vlachova V (2009) Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel. Biochim Biophys Acta 1793:1279–1288
Bessac BF, Jordt S-E (2008) Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control. Physiology (Bethesda) 23:360–370
Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt SE (2009) Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J 23:1102–1114
Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Investig 118:1899–1910
Bianchi BR, Zhang XF, Reilly RM, Kym PR, Yao BB, Chen J (2012) Species comparison and pharmacological characterization of human, monkey, rat and mouse TRPA1 channels. J Pharmacol Exp Ther 341:360–368
Binder A, May D, Baron R, Maier C, Tolle TR, Treede RD, Berthele A, Faltraco F, Flor H, Gierthmuhlen J, Haenisch S, Huge V, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Uceyler N, Ufer M, Wasner G, Zhu J, Cascorbi I (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS One 6:e17387
Bobkov YV, Corey EA, Ache BW (2011) The pore properties of human nociceptor channel TRPA1 evaluated in single channel recordings. Biochim Biophys Acta 1808:1120–1128
Brenneis C, Sisignano M, Coste O, Altenrath K, Fischer MJ, Angioni C, Fleming I, Brandes RP, Reeh PW, Woolf CJ, Geisslinger G, Scholich K (2011) Soluble epoxide hydrolase limits mechanical hyperalgesia during inflammation. Mol Pain 7:78
Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 589:3575–3593
Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O’Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T, Holtmann G, Corey DP, Rychkov GY, Blackshaw LA (2009) The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology 137:2084–2095
Brockhoff A, Behrens M, Massarotti A, Appendino G, Meyerhof W (2007) Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J Agric Food Chem 55:6236–6243
Brooks SM (2010) Occupational, environmental, and irritant-induced cough. Otolaryngol Clin North Am 43:85–96
Brooks SM, Bernstein IL (2011) Irritant-induced airway disorders. Immunol Allergy Clin North Am 31:747–768
Brownlee M (2011) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820
Brozmanova M, Mazurova L, Ru F, Tatar M, Kollarik M (2012) Comparison of TRPA1-versus TRPV1- mediated Cough in Guinea Pigs. Eur J Pharmacol 689:211–218
Brozmanova M, Ru F, Surdenikova L, Mazurova L, Taylor-Clark T, Kollarik M (2011) Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists in the guinea pig esophagus. Neurogastroenterol Motil 23:e437–e445
Byers MR, Westenbroek RE (2011) Odontoblasts in developing, mature and ageing rat teeth have multiple phenotypes that variably express all nine voltage-gated sodium channels. Arch Oral Biol 56:1199–1220
Caceresa AI, Brackmann M, Elia MD, Bessac BF, del Caminob D, D’Amours M, Witek JS, Fanger CM, Chong JA, Hayward NJ, Homer RJ, Cohn L, Huang X, Moran MM, Jordt S-E (2009) A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci (USA) 106:9099–9104
Cao DS, Zhong L, Hsieh TH, Abooj M, Bishnoi M, Hughes L, Premkumar LS (2012) Expression of Transient Receptor Potential Ankyrin 1 (TRPA1) and Its Role in Insulin Release from Rat Pancreatic Beta Cells. PLoS One 7:e38005
Caspani O, Heppenstall PA (2009) TRPA1 and Cold Transduction: An Unresolved Issue? J Gen Physiol 133:245–249
Caterina MJ (2007) Chemical biology: Sticky spices. Nature 445:491–492
Cattaruzza F, Spreadbury I, Miranda-Morales M, Grady EF, Vanner SJ, Bunnett NW (2010) Transient Receptor Potential Ankyrin-1 has a Major Role in Mediating Visceral Pain in Mice. Am J Physiol Gastrointest Liver Physiol 298:G81–G91
Cavanaugh EJ, Simkin D, Kim D (2008) Activation of TRPA1 by Mustard oil, Tetrahydrocannabinol and Ca2+ Reveals Different Functional States of TRPA1. Neuroscience 154:1467–1476
Chatzigeorgiou M, Yoo S, Watson JD, Lee W-H, Spencer WC, Kindt KS, Hwang SW, Miller DM, Treinin M, Driscoll M, Schafer WR (2010) Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci 13:861–868
Chen J, Joshi SK, Didomenico S, Perner RJ, Mikusa JP, Gauvin DM, Segreti JA, Han P, Zhang XF, Niforatos W, Bianchi BR, Baker SJ, Zhong C, Simler GH, McDonald HA, Schmidt RG, McGaraughty SP, Chu KL, Faltynek CR, Kort ME, Reilly RM, Kym PR (2011) Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 152:1165–1172
Chen J, Kim D, Bianchi BR, Cavanaugh EJ, Faltynek CR, Kym PR, Reilly RM (2009) Pore dilation occurs in TRPA1 but not in TRPM8 channels. Mol Pain 5:3
Chen J, Zhang XF, Kort ME, Huth JR, Sun C, Miesbauer LJ, Cassar SC, Neelands T, Scott VE, Moreland RB, Reilly RM, Hajduk PJ, Kym PR, Hutchins CW, Faltynek CR (2008) Molecular determinants of species-specific activation or blockade of TRPA1 channels. J Neurosci 28:5063–5071
Cho JH, Jeong MY, Choi IS, Lee HJ, Jang IS (2012) TRPA1-like channels enhance glycinergic transmission in medullary dorsal horn neurons. J Neurochem 122:691–701
Choi MJ, Jin Z, Park YS, Rhee YK, Jin YH (2011) Transient receptor potential (TRP) A1 activated currents in TRPV1 and cholecystokinin-sensitive cranial visceral afferent neurons. Brain Res 1383:36–42
Christianson JA, Bielefeldt K, Malin SA, Davis BM (2010) Neonatal colon insult alters growth factor expression and TRPA1 responses in adult mice. Pain 151:540–549
Ciobanu C, Reid G, Babes A (2009) Acute and chronic effects of neurotrophic factors BDNF and GDNF on responses mediated by thermo-sensitive TRP channels in cultured rat dorsal root ganglion neurons. Brain Res 1284:54–67
Clapham DE, Nilius B, Owsianik G (2009) Transient receptor potential channels. Last modified on 2009-10-14. (IUPHAR-DB). http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId=78
Cordero-Morales JF, Gracheva EO, Julius D (2011) Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc Natl Acad Sci U S A 108:E1184–E1191
Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Geleoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432:723–730
Cruz-Orengo L, Dhaka A, Heuermann RJ, Young TJ, Montana MC, Cavanaugh EJ, Kim D, Story GM (2008) Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1. Mol Pain 4:30
Cvetkov TL, Huynh KW, Cohen MR, Moiseenkova-Bell VY (2011) Molecular architecture and subunit organization of TRPA1 channel revealed by electron microscopy. J Biol Chem 286:38168–38176
Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H, Noguchi K (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Investig 117:1978–1987
De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V (2010) Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 163:1479–1494
De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 (TRPA1) and melastatin type-8 (TRPM-8). J Pharmacol Exp Ther 325:1007–1015
Defalco J, Steiger D, Gustafson A, Emerling DE, Kelly MG, Duncton MA (2010) Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor. Bioorg Med Chem Lett 20:276–279
Deffontaines Rufin S, Jousse M, Verollet D, Guinet A, Ismael SS, Amarenco G (2010) Cold perception of the bladder during ice water test. Study on 120 patients. Ann Phys Rehabil Med 53:559–567
Del Camino D, Murphy S, Heiry M, Barrett LB, Earley TJ, Cook CA, Petrus MJ, Zhao M, D’Amours M, Deering N, Brenner GJ, Costigan M, Hayward NJ, Chong JA, Fanger CM, Woolf CJ, Patapoutian A, Moran MM (2010) TRPA1 Contributes to Cold Hypersensitivity. J Neurosci 30:15165–15174
Deshpande DA, Wang CH, Mcilmoyle EI, Robinett KS, Schillinger RM, An SS, Sham JSK, Ligget SB (2010) Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat Med 16:1299–1305
Ding Z, Gomez T, Werkheiser JL, Cowan A, Rawls SM (2007) Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation. Eur J Pharmacol 578:201–208
Diogenes A, Akopian AN, Hargreaves KM (2007) NGF up-regulates TRPA1: implications for orofacial pain. J Dent Res 86:550–555
Doerner JF, Gisselmann G, Hatt H, Wetzel CH (2007) Transient receptor potential channel A1 is directly gated by calcium ions. J Biol Chem 282:13180–13189
Doihara H, Nozawa K, Kawabata-Shoda E, Kojima R, Yokoyama T, Ito H (2009) TRPA1 agonists delay gastric emptying in rats through serotonergic pathways. Naunyn Schmiedebergs Arch Pharmacol 80:353–357
Dong Y, Shi HL, Shi JR, Wu DZ (2010) Transient receptor potential A1 is involved in cold-induced contraction in the isolated rat colon smooth muscle. Sheng Li Xue Bao 62:349–356
Du S, Araki I, Kobayashi H, Zakoji H, Sawada N, Takeda M (2008) Differential Expression Profile of Cold (TRPA1) and Cool (TRPM8) Receptors in Human Urogenital Organs. Urology 72:450–455
Du S, Araki I, Yoshiyama M, Nomura T, Takeda M (2007) Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology 70:826–831
Dunham JP, Kelly S, Donaldson LF (2008) Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1-expressing nociceptors in the rat. Eur J Neurosci 27:3151–3160
Dunham JP, Leith JL, Lumb BM, Donaldson LF (2010) Transient Receptor Potential Channel A1 and noxious cold responses in rat cutaneous nociceptors. Neuroscience 165:412–1419
Earley S (2012) TRPA1 Channels in the Vasculature. Br J Pharmacol 167:13–22
Earley S, Gonzales AL, Crnich R (2009) Endothelium-Dependent Cerebral Artery Dilation Mediated by TRPA1 and Ca2 + -Activated K + Channels. Circ Res 104:987–U166
Eberhardt MJ, Filipovic MR, Leffler A, de la Roche J, Kistner K, Fleming T, Zimmermann K, Ivanovic-Burmazovic I, Nawroth PP, Bierhaus A, Reeh PW, Sauer SK (2012) Methylglyoxal activates nociceptors through TRPA1 - a possible mechanism of metabolic neuropathies. J Biol Chem 287:28291–28306
Edelmayer RM, Le LN, Yan J, Wei X, Nassini R, Materazzi S, Preti D, Appendino G, Geppetti P, Dodick DW, Vanderah TW, Porreca F, Dussor G (2012) Activation of TRPA1 on dural afferents: A potential mechanism of headache pain. Pain 153:1949–1958
El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Killough SA, Lundy FT (2011) Human Dental Pulp Fibroblasts Express the “Cold-sensing” Transient Receptor Potential Channels TRPA1 and TRPM8. J Endod 37:473–478
El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Lundy FT (2011) Human odontoblasts express functional thermo-sensitive TRP channels: Implications for dentin sensitivity. Pain 152:2211–2223
Elitt CM, Malin SA, Koerber HR, Davis BM, Albers KM (2008) Overexpression of artemin in the tongue increases expression of TRPV1 and TRPA1 in trigeminal afferents and causes oral sensitivity to capsaicin and mustard oil. Brain Res 1230:80–90
Elitt CM, McIlwrath SL, Lawson JJ, Malin SA, Molliver DC, Cornuet PK, Koerber HR, Davis BM, Albers KM (2006) Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. J Neurosci 26:8578–8587
Engel MA, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipovic MR, Izydorczyk I, Eberhardt M, Kichko TI, Mueller-Tribbensee SM, Khalil M, Siklosi N, Nau C, Ivanovic-Burmazovic I, Neuhuber WL, Becker C, Neurath MF, Reeh PW (2011) TRPA1 and Substance P Mediate Colitis in Mice. Gastroenterology 141:1346–1358
Escalera J, von Hehn CA, Bessac BF, Sivula M, Jordt SE (2008) TRPA1 mediates the noxious effects of natural sesquiterpene deterrents. J Biol Chem 283:24136–24144
Fajardo O, Meseguer V, Belmonte C, Viana F (2008) TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: pharmacological and genetic evidence. J Neurosci 28:7863–7875
Fajardo O, Meseguer V, Belmonte C, Viana F (2008) TRPA1 channels: Novel targets of 1,4-dihydropyridines. Channels (Austin) 2:429–438
Fernandes ES, Russell FA, Spina D, McDougall JJ, Graepel R, Gentry C, Staniland AA, Mountford DM, Keeble JE, Malcangio M, Bevan S, Brain SD (2011) A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor alpha-induced inflammatory hyperalgesia and Freund’s complete adjuvant-induced monarthritis. Arthritis Rheum 63:819–829
Fischer MJ, Leffler A, Niedermirtl F, Kistner K, Eberhardt M, Reeh PW, Nau C (2010) The General Anesthetic Propofol Excites Nociceptors by Activating Trpv1 and Trpa1 Rather Than Gabaa Receptors. J Biol Chem 285:34781–34792
Forster AB, Reeh PW, Messlinger K, Fischer MJ (2009) High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors. Mol Pain 5:17
Franck MC, Stenqvist A, Li L, Hao J, Usoskin D, Xu X, Wiesenfeld-Hallin Z, Ernfors P (2011) Essential role of Ret for defining non-peptidergic nociceptor phenotypes and functions in the adult mouse. Eur J Neurosci 33:1385–1400
Fujita F, Moriyama T, Higashi T, Shima A, Tominaga M (2007) Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels. Br J Pharmacol 151:153–160
Fujita T, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M (2008) Intracellular alkalinization causes pain sensation through activation of TRPA1. J Clin Investig 118:4049–4057
Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N (2012) Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: Implication for the pathogenesis of interstitial cystitis/bladder pain syndrome. Int J Urol Off J Jpn Urological Assoc 19:429–436
Garrison SL, Stucky CL (2011) The Dynamic TRPA1 Channel: A Suitable Pharmacological Pain Target? Curr Pharm Biotechnol 12:1689–1697
Garrity PA (2011) Weakly acidic, but strongly irritating: TRPA1 and the activation of nociceptors by cytoplasmic acidification. J Gen Physiol 137:489–491
Gees M, Colsoul B, Nilius B (2010) The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling. Cold Spring Harb Perspect Biol 2:a003962
Geng J, Liang D, Jiang K, Zhang P (2012) Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies. PLoS One 6:e28644
Gentry C, Stoakley N, Andersson DA, Bevan S (2010) The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity. Mol Pain 6:4
Ghiani A, Aina R, Asero R, Bellotto E, Citterio S (2012) Ragweed pollen collected along high-traffic roads shows a higher allergenicity than pollen sampled in vegetated areas. Allergy 67:887–894
Gijsen HJ, Berthelot D, Zaja M, Brone B, Geuens I, Mercken M (2010) Analogues of Morphanthridine and the Tear Gas Dibenz[b, f][1,4]oxazepine (CR) as Extremely Potent Activators of the Human Transient Receptor Potential Ankyrin 1 (TRPA1) Channel. J Med Chem 53:7011–7020
Grace MS, Belvisi MG (2010) TRPA1 receptors in Cough. Pulm Pharmacol Ther 24:286–288
Grace M, Birrell MA, Dubuis E, Maher SA, Belvisi MG (2012) Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax 67:891–900
Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sanchez EE, Perez JC, Weissman JS, Julius D (2010) Molecular basis of infrared detection by snakes. Nature 464:1006–1012
Gratzke C, Weinhold P, Reich O, Seitz M, Schlenker B, Stief CG, Andersson KE, Hedlund P (2010) Transient Receptor Potential A1 and Cannabinoid Receptor Activity in Human Normal and Hyperplastic Prostate: Relation to Nerves and Interstitial Cells. Eur Urol 57:902–910
Gregus AM, Doolen S, Dumlao DS, Buczynski MW, Takasusuki T, Fitzsimmons BL, Hua XY, Taylor BK, Dennis EA, Yaksh TL (2012) Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors. Proc Natl Acad Sci U S A 109:6721–6726
Gu Q, Lin RL (2010) Heavy metals zinc, cadmium and copper stimulate pulmonary sensory neurons via direct activation of TRPA1. J Appl Physiol 108:891–897
Haas ET, Rowland K, Gautam M (2011) Tooth injury increases expression of the cold sensitive TRP channel TRPA1 in trigeminal neurons. Arch Oral Biol 56:1604–1609
Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, Garrity PA (2008) An internal thermal sensor controlling temperature preference in Drosophila. Nature 454:217–220
Hatano N, Itoh Y, Suzuki H, Muraki Y, Hayashi H, Onozaki K, Wood IC, Beech DJ, Muraki K (2012) HIF1alpha switches on TRPA1 gene expression via a hypoxia response element-like motif to modulate cytokine release. J Biol Chemistry in the press
Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cellular and Molecular Life Sciences: CMLS 65:1631–1652
Hazari MS, Haykal-Coates N, Winsett DW, Krantz QT, King C, Costa DL, Farraj AK (2011) TRPA1 and Sympathetic Activation Contribute to Increased Risk of Triggered Cardiac Arrhythmias in Hypertensive Rats Exposed to Diesel Exhaust. Environ Heal Perspect 119:951–957
Hermanstyne TO, Markowitz K, Fan L, Gold MS (2008) Mechanotransducers in rat pulpal afferents. J Dent Res 87:834–838
Hill K, Schaefer M (2007) TRPA1 is differentially modulated by the amphiphatic molecules trinitrophenol and chlorpromazine. J Biol Chem 282:7145–7153
Hill K, Schaefer M (2008) Ultraviolet light and photosensitising agents activate TRPA1 via generation of oxidative stress. Cell Calcium 45:55–164
Hinman A, Chuang H-H, Bautista DM, Julius D (2007) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci (USA) 103:19564–19568
Hjerling-Leffler J, Alqatari M, Ernfors P, Koltzenburg M (2007) Emergence of functional sensory subtypes as defined by transient receptor potential channel expression. J Neurosci 27:2435–2443
Hu H, Bandell M, Petrus MJ, Zhu MX, Patapoutian A (2009) Zinc activates damage-sensing TRPA1 ion channels. Nat Chem Biol 5:183–190
Hu H, Tian J, Zhu Y, Wang C, Xiao R, Herz JM, Wood JD, Zhu MX (2010) Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs. Pflugers Arch Europ J Physiol 459:579–592
Hwang RY, Stearns NA, Tracey WD (2012) The Ankyrin Repeat Domain of the TRPA Protein Painless Is Important for Thermal Nociception but Not Mechanical Nociception. PLoS One 7:e30090
Inoue M, Fujita T, Goto M, Kumamoto E (2012) Presynaptic enhancement by eugenol of spontaneous excitatory transmission in rat spinal substantia gelatinosa neurons is mediated by transient receptor potential A1 channels. Neuroscience 210:403–415
Inoue N, Ito S, Nogawa M, Tajima K, Kyoi T (2012) Etodolac Blocks the Allyl Isothiocyanate-Induced Response in Mouse Sensory Neurons by Selective TRPA1 Activation. Pharmacology 90:47–54
Iwasaki Y, Tanabe M, Kayama Y, Abe M, Kashio M, Koizumi K, Okumura Y, Morimitsu Y, Tominaga M, Ozawa Y, Watanabe T (2009) Miogadial and miogatrial with alpha, beta-unsaturated 1,4-dialdehyde moieties-novel and potent TRPA1 agonists. Life Sci 85:60–69
Jain A, Bronneke S, Kolbe L, Stab F, Wenck H, Neufang G (2011) TRP-channel-specific cutaneous eicosanoid release patterns. Pain 152:2765–2772
Jaquemar D, Schenker T, Trueb B (1999) An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem 274:7325–7333
Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265
Kaji I, Karaki SI, Kuwahara A (2011) Effects of luminal thymol on epithelial transport in human and rat colon. Am J Physiol Gastrointest Liver Physiol 300:G1132–G1143
Kaji I, Yasuoka Y, Karaki SI, Kuwahara A (2012) Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon. Am J Physiol Gastrointest Liver Physiol 302:G690–G701
Kang K, Panzano VC, Chang EC, Ni L, Dainis AM, Jenkins AM, Regna K, Muskavitch MA, Garrity PA (2012) Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila. Nature 481:76–80
Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL, Garrity PA (2010) Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature 464:597–U155
Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci 27:9874–9884
Karashima Y, Prenen J, Meseguer V, Owsianik G, Voets T, Nilius B (2008) Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators. Pflügers Arch Eur J Physiol 457:77–89
Karashima Y, Prenen J, Talavera K, Janssens A, Voets T, Nilius B (2010) Agonist-Induced Changes in Ca(2+) Permeation through the Nociceptor Cation Channel TRPA1. Biophys J 98:773–783
Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, Nilius B, Voets T (2009) TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci U S A 106:1273–1278
Kerstein PC, Del Camino D, Moran MM, Stucky CL (2009) Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors. Mol Pain 5:19
Kim D, Cavanaugh EJ (2007) Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates. J Neurosci 27:6500–6509
Kim D, Cavanaugh E, Simkin D (2009) Inhibition of Transient Receptor Potential A1 by Phosphatidylinositol-4,5-bisphosphate. Amer J Physiol Cell Physiology 295:C92–C99
Kim YS, Jung HK, Kwon TK, Kim CS, Cho JH, Ahn DK, Bae YC (2012) Expression of Transient Receptor Potential Ankyrin 1 in Human Dental Pulp. J Endod 38:1087–1092
Kim SH, Lee Y, Akitake B, Woodward OM, Guggino WB, Montell C (2010) Drosophila TRPA1 channel mediates chemical avoidance in gustatory receptor neurons. Proc Natl Acad Sci U S A 107:8440–8445
Kim YS, Son JY, Kim TH, Paik SK, Dai Y, Noguchi K, Ahn DK, Bae YC (2009) Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn. J Comp Neurol 518:687–698
Kimball ES, Prouty SP, Pavlick KP, Wallace NH, Schneider CR, Hornby PJ (2007) Stimulation of neuronal receptors, neuropeptides and cytokines during experimental oil of mustard colitis. Neurogastroenterol Motil 19:390–400
Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (2007) Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci 10:568–577
Klein AH, Sawyer CM, Zanotto KL, Ivanov MA, Cheung S, Iodi Carstens M, Furrer S, Simons CT, Slack JP, Carstens E (2011) A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats. J Neurophysiol 105:1701–1710
Koch M, Kreutz S, Bottger C, Grabiec U, Ghadban C, Korf HW, Dehghani F (2010) The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB(1) receptors and modulated by TRPA1 and Ca(v)2.2 channels. Hippocampus 21:554–564
Kohno K, Sokabe T, Tominaga M, Kadowaki T (2010) Honey Bee Thermal/Chemical Sensor, AmHsTRPA, Reveals Neofunctionalization and Loss of Transient Receptor Potential Channel Genes. J Neurosci 30:12219–12229
Koivisto A (2012) Sustained TRPA1 activation in vivo. Acta Physiol 204:248–254
Kollarik M, Brozmanova M (2009) Cough and gastroesophageal reflux: Insights from animal models. Pulm Pharmacol Ther 22:130–134
Komatsu T, Uchida K, Fujita F, Zhou Y, Tominaga M (2012) Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner. Pflugers Archiv Eur J Physiol 463:549–559
Kondo T, Obata K, Miyoshi K, Sakurai J, Tanaka J, Miwa H, Noguchi K (2009) Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats. Gut 58:1342–1352
Koo JY, Jang Y, Cho H, Lee CH, Jang KH, Chang YH, Shin J, Oh U (2007) Hydroxy-alpha-sanshool activates TRPV1 and TRPA1 in sensory neurons. Eur J Neurosci 26:1139–1147
Koseki J, Oshima T, Kondo T, Tomita T, Fukui H, Watari J, Hattori T, Kase Y, Miwa H (2012) Role of transient receptor potential ankyrin 1 in gastric accommodation in conscious guinea pigs. J Pharmacol Exp Ther 341:205–212
Kosugi M, Natatsuka T, Fujita T, Kuroda Y, Kummamoto E (2007) Activation of TRPA1 channel fascilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord. J Neurosci 27:4443–4451
Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR, Villegas A, Acosta N, Pineda-Trujillo NG, Ramírez JD, Zea J, Burley M-W, Bedoya G, Bennett DLH, Wood JN, Ruiz-Linares A (2010) A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome. Neuron 66:671–680
Kunkler PE, Ballard CJ, Oxford GS, Hurley JH (2010) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain 152:38–44
Kurogi M, Miyashita M, Emoto Y, Kubo Y, Saitoh O (2012) Green Tea Polyphenol Epigallocatechin Gallate Activates TRPA1 in an Intestinal Enteroendocrine Cell Line, STC-1. Chem Senses 37:167–177
Kwan KY, Corey DP (2009) Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation. J Gen Physiol 133:251–256
Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 29:4808–4819
Kwon Y, Shim HS, Wang X, Montell C (2008) Control of thermotactic behavior via coupling of a TRP channel to a phospholipase C signaling cascade. Nat Neorsci 11:871–873
La JH, Schwartz ES, Gebhart GF (2011) Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K(+) channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder and colon. Neuroscience 186:179–187
Latorre R (2009) Perspectives on TRP Channel Structure and the TRPA1 Puzzle. J Gen Physiol 133:227–229
Leamy AW, Shukla P, McAlexander MA, Carr MJ, Ghatta S (2011) Curcumin ((E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) activates and desensitizes the nociceptor ion channel TRPA1. Neurosci Lett 503:157–162
Lee SP, Buber T, Yang Q, Cerne R, Corte’s RY, Sprous DG, Bryant RW (2008) Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol 153:1739–1749
Lefer DJ (2007) A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide. Proc Natl Acad Sci U S A 104:17907–17908
Leffler A, Lattrell A, Kronewald S, Niedermirtl F, Nau C (2011) Activation of TRPA1 by membrane permeable local anesthetics. Mol Pain 7:62
Li L, Bhatia M, Moore PK (2006) Hydrogen sulphide–a novel mediator of inflammation? Curr Opin Pharmacol 6:125–129
Liang J, Bi H, Ji W (2010) Involvement of TRPA1 in ET-1-induced pain-like behavior in mice. Neuroreport 21:201–205
Liu T, Ji RR (2012) Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice. Neurosci Bull 28:145–154
Liu K, Samuel M, Ho M, Harrison RK, Paslay JW (2010) NPPB structure-specifically activates TRPA1 channels. Biochem Pharmacol 80:113–121
Macho A, Lucena C, Sancho R, Daddario N, Minassi A, Munoz E, Appendino G (2003) Non-pungent capsaicinoids from sweet pepper. Synthesis and evaluation of their chemopreventive and anticancer potential. Eur J Nutr 42:2–9
Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541–545
Macpherson L, Geierstanger BH, Viswanath V, Bandell M, Eid SR, Patapoutian A (2005) The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr Biol 15:929–934
Macpherson LJ, Patapoutian A (2010) Channels: Flies feel your pain. Nat Chem Biol 6:252–253
Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang SW, Cravatt B, Corey DP, Patapoutian A (2007) An Ion Channel Essential for Sensing Chemical Damage. J Neurosci 27:11412–11415
Maher M, Ao H, Banke T, Nasser N, Wu N-T, Breitenbucher G, Chaplan SR, Wickenden AD (2008) Activation of TRPA1 by farnesyl thiosalicylic acid, disulfiram and chlordantoin. Mol Pharmacol 73:1225–1234
Maher SA, Dubuis ED, Belvisi MG (2011) G-protein coupled receptors regulating cough. Curr Opin Pharmacol 11:248–253
Maione S, Piscitelli F, Gatta L, Vita D, De Petrocellis L, Palazzo E, De Novellis V, Di Marzo V (2011) Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetised rats through several mechanisms of action. Br J Pharmacol 162:584–596
Malin SA, Molliver DC, Koerber HR, Cornuet P, Frye R, Albers KM, Davis BM (2006) Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci 26:8588–8599
Markowitz K (2009) Pretty painful: Why does tooth bleaching hurt? Med Hypotheses 74:835–840
Masamoto Y, Kawabata F, Fushiki T (2009) Intragastric Administration of TRPV1, TRPV3, TRPM8, and TRPA1 Agonists Modulates Autonomic Thermoregulation in Different Manners in Mice. Biosci Biotechnol Biochem 73:1021–1027
Materazzi S, Fusi C, Benemei S, Pedretti P, Patacchini R, Nilius B, Prenen J, Creminon C, Geppetti P, Nassini R (2012) TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch - Eur J Physiol 463:561–569
Materazzi S, Nassini R, Andre E, Campi B, Amadesi S, Trevisani M, Bunnett NW, Patacchini R, Geppetti P (2008) Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 105:12045–12050
Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP (2008) General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci (USA) 105:8784–8789
May D, Baastrup J, Nientit MR, Binder A, Schuenke M, Baron R, Cascorbi I (2012) Differential expression and functionality of TRPA1 genetic variants in conditions of thermal stimulation. J Biol Chem 287:27087–27094
McGaraughty S, Chu KL, Perner RJ, Didomenico S, Kort ME, Kym PR (2010) TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Mol Pain 6:14
McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A 104:13525–13530
Menozzi-Smarrito C, Riera CE, Munari C, Le Coutre J, Robert F (2009) Synthesis and Evaluation of New Alkylamides Derived from alpha-Hydroxysanshool, the Pungent Molecule in Szechuan Pepper. J Agric Food Chem 57:1982–1989
Michel MC (2007) Editorial Comment on: Distribution and Function of the Hydrogen Sulfide-Sensitive TRPA1 Ion Channel in Rat Urinary Bladder. Eur Urol 53:399–400
Miyamoto T, Dubin AE, Petrus MJ, Patapoutian A (2009) TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLoS One 4:e7596
Miyamoto R, Otsuguro KI, Ito S (2011) Time- and concentration-dependent activation of TRPA1 by hydrogen sulfide in rat DRG neurons. Neurosci Lett 499:137–142
Mizushima T, Obata K, Katsura H, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Mashimo T, Noguchi K (2006) Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons. Neuroscience 140:1337–1348
Morera E, De Petrocellis L, Morera L, Schiano Moriello A, Nalli M, Di Marzo V, Ortar G (2012) Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators. Bioorg Med Chem Lett 22:1674–1677
Motter AL, Ahern GP (2012) TRPA1 Is a Polyunsaturated Fatty Acid Sensor in Mammals. PLoS One 7:e38439
Mukhopadhyay I, Gomes P, Aranake S, Shetty M, Karnik P, Damle M, Kuruganti S, Thorat S, Khairatkar-Joshi N (2011) Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res 31:350–358
Nagata K, Duggan A, Kumar G, Garcia-Anoveros J (2005) Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci 25:4052–4061
Nagatomo K, Ishii H, Yamamoto T, Nakajo K, Kubo Y (2010) The Met268Pro Mutation of Mouse TRPA1 Changes the Effect of Caffeine from Activation to Suppression. Biophys J 99:3609–3618
Nagatomo K, Kubo Y (2008) Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels. Proc Natl Acad Sci U S A 105:17373–17378
Namer B, Seifert F, Handwerker HO, Maihofner C (2005) TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport 16:955–959
Narukawa M, Koizumi K, Iwasaki Y, Kubota K, Watanabe T (2010) Galangal Pungent Component, 1′-Acetoxychavicol Acetate, Activates TRPA1. Biosci Biotechnol Biochem 74:1694–1696
Nassenstein C, Kwong KK, Taylor-Clark TE, Kollarik M, Macglashan DW, Braun A, Undem BJ (2008) TRPA1 Expression and Function in Vagal Afferent Nerves Innervating Mouse Lungs. J Physiol 586:1595–1604
Nassini R, Gees M, Harrison S, De Siena G, Materazzi S, Moretto N, Failli P, Preti D, Marchetti N, Cavazzini A, Mancini F, Pedretti P, Nilius B, Patacchini R, Geppetti P (2011) Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain 152:1621–1631
Nassini R, Materazzi S, Andre E, Sartiani L, Aldini G, Trevisani M, Carnini C, Massi D, Pedretti P, Carini M, Cerbai E, Preti D, Villetti G, Civelli M, Trevisan G, Azzari C, Stokesberry S, Sadofsky L, McGarvey L, Patacchini R, Geppetti P (2010) Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents. FASEB J 24:4904–4916
Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S, De Siena G, la Marca G, Andre E, Preti D, Avonto C, Sadofsky L, Di Marzo V, De Petrocellis L, Dussor G, Porreca F, Taglialatela-Scafati O, Appendino G, Nilius B, Geppetti P (2012) The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system. Brain 135:376–390
Neely GG, Keene AC, Duchek P, Chang EC, Wang QP, Aksoy YA, Rosenzweig M, Costigan M, Woolf CJ, Garrity PA, Penninger JM (2011) TrpA1 Regulates Thermal Nociception in Drosophila. PLoS One 6:e24343
Negri L, Lattanzi R, Giannini E, Canestrelli M, Nicotra A, Melchiorri P (2009) Chapter 11 Bv8/Prokineticins and their Receptors A New Pronociceptive System. Int Rev Neurobiol 85:145–157
Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12:218–229
Nilius B, Owsianik G, Voets T (2008) Transient receptor potential channels meet phosphoinositides. EMBO J 27:2809–2816
Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient Receptor Potential Channels in Disease. Physiol Rev 87:165–217
Nilius B, Prenen J, Owsianik G (2011) Irritating Channels: the case of TRPA1. J Physiol 589:1543–1549
Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, Sano Y, Inamura K, Matsushime H, Koizumi T, Yokoyama T, Ito H (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A 106:3408–3413
Numazawa S, Takase M, Ahiko T, Ishii M, Shimizu S, Yoshida T (2012) Possible Involvement of Transient Receptor Potential Channels in Electrophile-Induced Insulin Secretion from RINm5F Cells. Biol Pharm Bull 35:346–354
Ogawa H, Takahashi K, Miura S, Imagawa T, Saito S, Tominaga M, Ohta T (2012) H(2)S Functions as a Nociceptive Messenger Through Transient Receptor Potential Ankyrin 1 (Trpa1) Activation. Neuroscience 218:335–343
Okubo K, Matsumura M, Kawaishi Y, Aoki Y, Matsunami M, Okawa Y, Sekiguchi F, Kawabata A (2012) Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Ca(v) 3.2 and TRPA1 channels in mice. Br J Pharmacol 166:1738–1743
Okumura Y, Narukawa M, Iwasaki Y, Ishikawa A, Matsuda H, Yoshikawa M, Watanabe T (2010) Activation of TRPV1 and TRPA1 by Black Pepper Components. Biosci Biotechnol Biochem 74:1068–1072
Panzano VC, Kang K, Garrity PA (2010) Infrared Snake Eyes: TRPA1 and the Thermal Sensitivity of the Snake Pit Organ. Sci Signal 3:pe22
Patacchini R, Santicioli P, Giuliani S, Maggi CA (2005) Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle. Eur J Pharmacol 509:171–177
Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4:529–539
Patil MJ, Belugin S, Akopian AN (2011) Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses. J Neurosci Res 89:945–954
Patil MJ, Jeske NA, Akopian AN (2010) TRPV1 regulates activation and modulation of TRPA1 by Ca2+. Neuroscience 171:1109–1119
Patil M, Patwardhan A, Salas MM, Hargreaves KM, Akopian AN (2011) Cannabinoid receptor antagonists AM251 and AM630 activate TRPA1 in sensory neurons. Neuropharmacology 61:778–788
Pecze L, Pelsoczi P, Kecskés M, Winter Z, Papp A, Kaszá K, Letoha L, Vizler C, Oláh Z (2009) Resiniferatoxin Mediated Ablation of TRPV1+ Neurons Removes TRPA1 as Well. Can J Neurol Sci 36:234–241
Pertovaara A, Koivisto A (2011) TRPA1 ion channel in the spinal dorsal horn as a therapeutic target in central pain hypersensitivity and cutaneous neurogenic inflammation. Eur J Pharmacol 666:1–4
Peterlin Z, Chesler A, Firestein S (2007) A painful Trp can be a bonding experience. Neuron 53:635–638
Peyrot des Gachons C, Uchida K, Bryant B, Shima A, Sperry JB, Dankulich-Nagrudny L, Tominaga M, Smith AB 3rd, Beauchamp GK, Breslin PA (2011) Unusual pungency from extra-virgin olive oil is attributable to restricted spatial expression of the receptor of oleocanthal. J Neurosci 31:999–1009
Piao L-H, Fujita T, Jiang C-Y, Liu T, Yue HY, Nakatsuka T, Kumamoto E (2009) TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase. Biochem Biophys Res Commun 379:980–984
Pollastro F, Taglialatela-Scafati O, Allara M, Munoz E, Di Marzo V, De Petrocellis L, Appendino G (2011) Bioactive Prenylogous Cannabinoid from Fiber Hemp (Cannabis sativa). J Nat Prod 74:2019–2022
Poole DP, Pelayo JC, Cattaruzza F, Kuo YM, Gai G, Chiu JV, Bron R, Furness JB, Grady EF, Bunnett NW (2011) Transient Receptor Potential Ankyrin 1 is Expressed by Inhibitory Motoneurons of the Mouse Intestine. Gastroenterology 141:565–U656
Pozsgai G, Bodkin JV, Graepel R, Bevan S, Andersson DA, Brain SD (2010) Evidence for the Pathophysiological Relevance of Trpa1 Receptors in the Cardiovascular System in Vivo. Cardiovasc Res 87:760–768
Pozsgai G, Hajna Z, Bagoly T, Boros M, Kemeny A, Materazzi S, Nassini R, Helyes Z, Szolcsanyi J, Pinter E (2012) The role of transient receptor potential ankyrin 1 (TRPA1) receptor activation in hydrogen-sulphide-induced CGRP-release and vasodilation. Eur J Pharmacol 689:56–64
Prober DA, Zimmerman S, Myers BR, McDermott BM Jr, Kim SH, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF (2008) Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. J Neurosci 28:10102–10110
Qian X, Francis M, Solodushko V, Earley S, Taylor MS (2012) Recruitment of Dynamic Endothelial Ca(2+) Signals by the TRPA1 Channel Activator AITC in Rat Cerebral Arteries. Microcirculation in the press
Raemdonck K, de Alba J, Birrell MA, Grace M, Maher SA, Irvin CG, Fozard JR, O’Byrne PM, Belvisi MG (2011) A role for sensory nerves in the late asthmatic response. Thorax 67:19–25
Rawls SM, Benamar K (2011) Effects of opioids, cannabinoids, and vanilloids on body temperature. Front Biosci (Schol Ed) 3:822–845
Rech JC, Eckert WA, Maher MP, Banke T, Bhattacharya A, Wickenden AD (2011) Recent advances in the biology and medicinal chemistry of TRPA1. Future Med Chem 2:843–858
Riera CE, Menozzi-Smarrito C, Affolter M, Michlig S, Munari C, Robert F, Vogel H, Simon SA, le Coutre J (2009) Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels. Brit J Pharm 157:1398–1409
Rodrigues MR, Kanazawa LK, Neves TL, Silva CF, Horst H, Pizzolatti MG, Santos AR, Baggio CH, Werner MF (2011) Antinociceptive and anti-inflammatory potential of extract and isolated compounds from the leaves of Salvia officinalis in mice. J Ethnopharmacol 139:519–526
Rubin BK (2007) Mucolytics, expectorants, and mucokinetic medications. Respir Care 52:859–865
Ruparel NB, Patwardhan AM, Akopian AN, Hargreaves KM (2011) Desensitization of TRPA1 by the TRPV1-selective cannabinoid arachidonoly-2chloroethanolamine (ACEA). Mol Pharmacol 80:117–123
Sadofsky LR, Boa AN, Maher SA, Birrell MA, Belvisi MG, Morice AH (2010) TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids. Pharmacol Res 63:30–36
Saito S, Nakatsuka K, Takahashi K, Fukuta N, Imagawa T, Ohta T, Tominaga M (2012) Analysis of Transient Receptor Potential Ankyrin 1 (TRPA1) in Frogs and Lizards Illuminates Both Nociceptive Heat and Chemical Sensitivities and Coexpression with TRP vanilloid 1 (TRPV1) in Ancestral Vertebrates. J Biol Chem 287:30743–30754
Salas MM, Hargreaves KM, Akopian AN (2009) TRPA1-mediated responses in trigeminal sensory neurons: interaction between TRPA1 and TRPV1. Europ J Neurosci 29:1568–1578
Samad A, Sura L, Benedikt J, Ettrich R, Minofar B, Teisinger J, Vlachova V (2011) The C-terminal basic residues contribute to the chemical and voltage-dependent activation of TRPA1. Biochem J 433:197–204
Saunders CJ, Silver WL (2008) The Respiratory Response of TRPV1 Knockout Mice to Trigeminal Irritants. Chem Senses 33:S104–S104
Sawada Y, Hosokawa H, Hori A, Matsumura K, Kobayashi S (2007) Cold sensitivity of recombinant TRPA1 channels. Brain Res 1160:39–46
Sawada Y, Hosokawa H, Matsumura K, Kobayashi S (2008) Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur J Neurosci 27:1131–1142
Schmidt M, Dubin AE, Petrus MJ, Earley TJ, Patapoutian A (2009) Nociceptive Signals Induce Trafficking of TRPA1 to the Plasma Membrane. Neuron 64:498–509
Schwartz ES, Christianson JA, Chen X, La JH, Davis BM, Albers KM, Gebhart GF (2011) Synergistic Role of TRPV1 and TRPA1 in Pancreatic Pain and Inflammation. Gastroenterology 140:140
Sculptoreanu A, Kullmann FA, Artim DE, Bazley FA, Schopfer F, Woodcock S, Freeman BA, de Groat W (2010) Nitro-oleic acid inhibits firing and activates TRPV1- and TRPA1-mediated inward currents in DRG neurons from adult male rats. J Pharmacol Exp Ther 333:883–895
Senatore S, Rami Reddy V, Semeriva M, Perrin L, Lalevee N (2010) Response to Mechanical Stress Is Mediated by the TRPA Channel Painless in the Drosophila Heart. PLoS Genet 6:e1001088, pii
Shigetomi E, Tong X, Kwan KY, Corey DP, Khakh BS (2012) TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neorsci 15:70–80
Shintaku K, Uchida K, Suzuki Y, Yiming Z, Fushiki T, Watanabe T, Yazawa S, Tominaga M (2012) Activation of TRPA1 by a non-pungent capsaicin-like compound, capsiate. Br J Pharmacol 165:1476–1486
Silva CR, Oliveira SM, Rossato MF, Dalmolin GD, Guerra GP, Prudente AD, Cabrini DA, Otuki MF, Andre E, Ferreira J (2011) The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice. Life Sci 88:1077–1087
Sisignano M, Park CK, Angioni C, Zhang DD, von Hehn C, Cobos EJ, Ghasemlou N, Xu ZZ, Kumaran V, Lu R, Grant A, Fischer MJ, Schmidtko A, Reeh P, Ji RR, Woolf CJ, Geisslinger G, Scholich K, Brenneis C (2012) 5,6-EET Is Released upon Neuronal Activity and Induces Mechanical Pain Hypersensitivity via TRPA1 on Central Afferent Terminals. J Neurosci 32:6364–6372
Smith MP, Beacham D, Ensor E, Koltzenburg M (2004) Cold-sensitive, menthol-insensitive neurons in the murine sympathetic nervous system. Neuroreport 15:1399–1403
Staruschenko A, Jeske NA, Akopian AN (2010) Contribution of TRPV1-TRPA1 interaction to the single-channel properties of the TRPA1 channel. J Biol Chem 85:15167–15177
Stepanyan RS, Indzhykulian AA, Velez-Ortega AC, Boger ET, Steyger PS, Friedman TB, Frolenkov GI (2011) TRPA1-Mediated Accumulation of Aminoglycosides in Mouse Cochlear Outer Hair Cells. J Assoc Res Otolaryngol Otolaryngol JARO 12:729–740
Stokes A, Wakano C, Koblan-Huberson M, Adra CN, Fleig A, Turner H (2006) TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD. Cell Signal 18:1584–1594
Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829
Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Hogestatt ED, Zygmunt PM (2008) Distribution and Function of the Hydrogen Sulfide-Sensitive TRPA1 Ion Channel in Rat Urinary Bladder. Eur Urol 53:391–399
Sun B, Bang SI, Jin YH (2009) Transient receptor potential A1 increase glutamate release on brain stem neurons. Neuroreport 20:1002–1006
Sun X, Ku DD (2006) Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats. Am J Physiol Heart Circ Physiol 291:H2431–H2438
Sun Y, Lei L, Ben-Shaharb Y, Jacobs JS, Eber DF, Welsh W, Welsh MJ (2009) TRPA channels distinguish gravity sensing from hearing in Johnston’s organ. Proc Nat Am Acad 106:13606–13611
Sura L, Zima V, Marsakova L, Hynkova A, Barvik I, Vlachova V (2012) C-terminal acidic cluster is involved in the Ca2 + -induced regulation of the human TRPA1 channel. J Biol Chem 287:18067–18077
Sviderskaya EV, Easty DJ, Lawrence MA, Sanchez DP, Negulyaev YA, Patel RH, Anand P, Korchev YE, Bennett DC (2009) Functional neurons and melanocytes induced from immortal lines of postnatal neural crest-like stem cells. FASEB J 23:3179–3192
Szabo C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6:917–935
Taglialatela-Scafati O, Pollastro F, Minassi A, Chianese G, De Petrocellis L, Di Marzo V, Appendino G (2012) Sesquiterpenoids from common ragweed (Ambrosia artemisiifolia L.) an invasive biological polluter. Eur J Org Chem in press; doi:10.1002/ejoc.201200650
Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y, Yamamoto S, Naito S, Knevels E, Carmeliet P, Oga T, Kaneko S, Suga S, Nokami T, Yoshida JI, Mori Y (2011) TRPA1 underlies a sensing mechanism for O(2). Nat Chem Biol 28:701–711
Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K, Mori Y (2008) Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels (Austin) 2:287–298
Takahashi N, Mori Y (2011) TRP Channels as Sensors and Signal Integrators of Redox Status Changes. Front Pharmacol 2:58
Takumida M, Ishibashi T, Hamamoto T, Hirakawa K, Anniko M (2008) Expression of transient receptor potential channel melastin (TRPM) 1-8 and TRPA1 (ankyrin) in mouse inner ear. Acta Otolaryngol 129:1050–1060
Talavera K, Gees M, Karashima Y, Meseguer VM, Vanoirbeek JA, Damann N, Everaerts W, Benoit M, Janssens A, Vennekens R, Viana F, Nemery B, Nilius B, Voets T (2009) Nicotine activates the chemosensory cation channel TRPA1. Nat Neorsci 12:1293–1299
Taylor-Clark TE, Ghatta S, Bettner W, Undem BJ (2009) Nitrooleic acid, an Endogenous Product of Nitrative Stress, Activates Nociceptive Sensory Nerves via the Direct Activation of TRPA1. Mol Pharmacol 75:820–829
Taylor-Clark TE, Kiros F, Carr MJ, McAlexander MA (2009) Transient Receptor Potential Ankyrin 1 Mediates Toluene Diisocyanate-Evoked Respiratory Irritation. Am J Respir Cell Mol Biol 40:756–762
Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ (2008) Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autocoid 4-oxononenal. J Physiol (Lond) 586:3447–3459
Taylor-Clark TE, Nassenstein C, McAlexander MA, Undem BJ (2008) TRPA1: A potential target for anti-tussive therapy. Pulm Pharmacol Ther 22:71–74
Taylor-Clark TE, Undem BJ (2010) Ozone activates airway nerves via the selective stimulation of TRPA1 ion channels. J Physiol (Lond) 588:423–433
Taylor-Clark TE, Undem BJ (2011) Sensing pulmonary oxidative stress by lung vagal afferents. Respir Physiol Neurobiol 178:406–413
Taylor-Clark TE, Undem BJ, Macglashan DW Jr, Ghatta S, Carr MJ, McAlexander MA (2008) Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol Pharmacol 73:274–281
Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andre E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P (2007) 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 104:13519–13524
Uchida K, Miura Y, Nagai M, Tominaga M (2012) Isothiocyanates from Wasabia japonica activate transient receptor potential ankyrin 1 channel. Chem Senses in the press
Undem BJ, Carr MJ (2010) Targeting primary afferent nerves for novel antitussive therapy. Chest 137:177–184
Uta D, Furue H, Pickering AE, Harunor Rashid M, Mizuguchi-Takase H, Katafuchi T, Imoto K, Yoshimura M (2010) TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord. Eur J Neurosci 31:1960–1973
Vilceanu D, Stucky CL (2010) TRPA1 Mediates Mechanical Currents in the Plasma Membrane of Mouse Sensory Neurons. PLoS One 5:e12177
Vriens J, Appendino G, Nilius B (2009) Pharmacology of vanilloid transient receptor potential cation channels Trpv. Mol Pharmacol 75:1262–1279
Wang YY, Chang RB, Allgood SD, Silver WL, Liman ER (2011) A TRPA1-dependent mechanism for the pungent sensation of weak acids. J Gen Physiol 137:493–505
Wang YY, Chang RB, Liman ER (2010) TRPA1 Is a Component of the Nociceptive Response to CO2. J Neurosci 30:12958–12963
Wang YY, Chang RB, Waters HN, McKemy DD, Liman ER (2008) The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J Biol Chem 283:32691–32703
Wang L, Cvetkov TL, Chance MR, Moiseenkova-Bell VY (2012) Identification of in vivo disulfide conformation of the TRPA1 ion channel. J Biol Chem 287:6169–6176
Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, Cui X, Tominaga M, Noguchi K (2008) Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain 131:1241–1251
Wang K, Guo Y, Wang F, Wang Z (2011) Drosophila TRPA Channel Painless Inhibits Male-Male Courtship Behavior through Modulating Olfactory Sensation. PLoS One 6:e25890
Wang S, Lee J, Ro JY, Chung MK (2012) Warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Mol Pain 8:22
Wang G, Qiu YT, Lu T, Kwon HW, Jason Pitts R, Van Loon JJ, Takken W, Zwiebel LJ (2009) Anopheles gambiae TRPA1 is a heat-activated channel expressed in thermosensitive sensilla of female antennae. Eur J Neurosci 30:967–974
Wang K, Zhao X, Chan S, Cil O, He N, Song X, Paterson AD, Pei Y (2009) Evidence for Pathogenicity of Atypical Splice Mutations in Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol 4:442–449
Wei H, Hamalainen MM, Saarnilehto M, Koivisto A, Pertovaara A (2009) Attenuation of Mechanical Hypersensitivity by an Antagonist of the TRPA1 Ion Channel in Diabetic Animals. Anesthesiology 111:147–154
Wei H, Karimaa M, Korjamo T, Koivisto A, Pertovaara A (2012) Transient Receptor Potential Ankyrin 1 Ion Channel Contributes to Guarding Pain and Mechanical Hypersensitivity in a Rat Model of Postoperative Pain. Anesthesiology 117:137–148
Wei H, Koivisto A, Saarnilehto M, Chapman H, Kuokkanen K, Hao B, Huang JL, Wang YX, Pertovaara A (2011) Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat. Pain 152:582–591
Weller K, Reeh PW, Sauer SK (2011) TRPV1, TRPA1, and CB1 in the isolated vagus nerve - Axonal chemosensitivity and control of neuropeptide release. Neuropeptides 45:391–400
White BJ, Smith PA, Dunn WR (2012) Hydrogen sulphide-mediated vasodilatation involves the release of neurotransmitters from sensory nerves in pressurized mesenteric small arteries isolated from rats. Br J Pharmacol in the press
Wilkinson JD, Kendall DA, Ralevic V (2007) Delta(9)-Tetrahydrocannabinol inhibits electrically-evoked CGRP release and capsaicin-sensitive sensory neurogenic vasodilatation in the rat mesenteric arterial bed. Br J Pharmacol 152:709–716
Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neorsci 14:595–602
Wood H (2010) Pain: new familial pain syndrome caused by TRPA1 mutation. Nat Rev Neurol 6:412
Wu LJ, Sweet TB, Clapham DE (2010) International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family. Pharmacol Rev 62:381–404
Xiao B, Dubin AE, Bursulaya B, Viswanath V, Jegla TJ, Patapoutian A (2008) Identification of the Transmembrane Domain Five as a Critical Molecular Determinant of Menthol Sensitivity in Mammalian TRPA1 Channels. J Neurosci 28:9640–9651
Xu H, Delling M, Jun JC, Clapham DE (2006) Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neorsci 9:628–635
Xu J, Sornborger AT, Lee JK, Shen P (2008) Drosophila TRPA channel modulates sugar-stimulated neural excitation, avoidance and social response. Nat Neurosci 11:676–682
Yang J, Li Y, Zuo X, Zhen Y, Yu Y, Gao L (2008) Transient receptor potential ankyrin-1 participates in visceral hyperalgesia following experimental colitis. Neurosci Lett 440:237–241
Yassaka RT, Inagaki H, Fujino T, Nakatani K, Kubo T, Mikoshiba K (2010) Enhanced Activation of the Transient Receptor Potential Channel TRPA1 by Ajoene, an Allicin Derivative. Neurosci Res 66:99–105
Ye Y, Dang D, Zhang J, Viet CT, Lam DK, Dolan J, Gibbs J, Schmidt BL (2011) Nerve growth factor links oral cancer progression, pain, and cachexia. Mol Cancer Ther 10:1667–1676
Yokoyama S, Altun A, Denardo DF (2011) Molecular Convergence of Infrared Vision in Snakes. Mol Biol Evol 28:45–48
Yokoyama T, Ohbuchi T, Saito T, Sudo Y, Fujihara H, Minami K, Nagatomo T, Uezono Y, Ueta Y (2011) Allyl isothiocyanates and cinnamaldehyde potentiate miniature excitatory postsynaptic inputs in the supraoptic nucleus in rats. Eur J Pharmacol 655:31–37
Yoshida N, Kobayashi K, Yu L, Wang S, Na R, Yamamoto S, Noguchi K, Dai Y (2011) Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin. Mol Pain 7:41
Yu S, Gao G, Peterson BZ, Ouyang A (2009) TRPA1 in Mast Cell Activation-induced Long-lasting Mechanical Hypersensitivity of Vagal Afferent C fibers in Guinea Pig Esophagus. Am J Physiol Gastrointest Liver Physiol 297:G34–G42
Yu S, Ouyang A (2008) TRPA1 in Bradykinin-induced Mechano-hypersensitivity of Vagal C Fibers in Guinea Pig Esophagus. Am J Physiol Gastrointest Liver Physiol 296:G255–G265
Yu YB, Yang J, Zuo XL, Gao LJ, Wang P, Li YQ (2010) Transient Receptor Potential Vanilloid-1 (TRPV1) and Ankyrin-1 (TRPA1) Participate in Visceral Hyperalgesia in Chronic Water Avoidance Stress Rat Model. Neurochem Res 35:797–803
Zanotto K, Merrill AW, Iodi Carstens M, Carstens E (2007) Neurons in superficial trigeminal subnucleus caudalis responsive to oral cooling, menthol and other irritant stimuli. J Neurophysiol 97:966–978
Zayats V, Samad A, Minofar B, Roelofs KE, Stockner T, Ettrich R (2012) Regulation of the transient receptor potential channel TRPA1 by its N-terminal ankyrin repeat domain. J Mol Model in the press
Zhang XF, Chen J, Faltynek CR, Moreland RB, Neelands TR (2008) Transient receptor potential A1 mediates an osmotically activated ion channel. Eur J Neurosci 27:605–611
Zhang H, Wickley PJ, Sinha S, Bratz IN, Damron DS (2011) Propofol Restores Transient Receptor Potential Vanilloid Receptor Subtype-1 Sensitivity via Activation of Transient Receptor Potential Ankyrin Receptor Subtype-1 in Sensory Neurons. Anesthesiology 114:1169–1179
Zhong L, Bellemer A, Yan H, Honjo K, Robertson J, Hwang RY, Pitt GS, Tracey WD (2012) Thermosensory and Nonthermosensory Isoforms of Drosophila melanogaster TRPA1 Reveal Heat-Sensor Domains of a ThermoTRP Channel. Cell Rep 1:43–55
Zhong J, Minassi A, Prenen J, Taglialatela-Scafati O, Appendino G, Nilius B (2011) Umbellulone modulates TRP channels. Pflügers Arch Eur J Physiol 462:861–870
Zhong J, Pollastro F, Prenen J, Zhu Z, Appendino G, Nilius B (2011) Ligustilide: a novel TRPA1 modulator. Pflugers Arch Eur J Physiol 462:841–849
Zhou Y, Sun B, Li Q, Luo P, Dong L, Rong W (2011) Sensitivity of bronchopulmonary receptors to cold and heat mediated by transient receptor potential cation channel subtypes in an ex vivo rat lung preparation. Respir Physiol Neurobiol 177:327–332
Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA (2007) Direct activation of the ion channel TRPA1 by Ca(2+). Nat Neorsci 10:277–279
Acknowldegments
We thank the members of the Laboratory of Ion Channel Research for helpful discussions. This work was supported by grants from the Belgian Federal Government (IUAP P5/05), the Research Foundation-Flanders (G.0172.03, G.0565.07 and G.0149.03), and the Research Council of the KU Leuven (GOA 2004/07 and EF/95/010).
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Nilius, B., Appendino, G. & Owsianik, G. The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch - Eur J Physiol 464, 425–458 (2012). https://doi.org/10.1007/s00424-012-1158-z
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DOI: https://doi.org/10.1007/s00424-012-1158-z