transient receptor potential channels


Summary: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN REPEATS are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.

Top Publications

  1. Spahn V, Stein C, Zöllner C. Modulation of transient receptor vanilloid 1 activity by transient receptor potential ankyrin 1. Mol Pharmacol. 2014;85:335-44 pubmed publisher
    ..This suggests that cross-sensitization of TRP channels contributes to enhanced pain sensitivity in inflamed tissues. ..
  2. Zhong J, Minassi A, Prenen J, Taglialatela Scafati O, Appendino G, Nilius B. Umbellulone modulates TRP channels. Pflugers Arch. 2011;462:861-70 pubmed publisher
    ..The lack of effects of the acetylated UMB derivatives suggests that steric hindrance may prevent access to the recognition site for the bicyclic monoterpene pharmacophore on TRPA1 and TRPM8. ..
  3. Son H, Kim M, Park J, Ishii S, Misaka T, Rhyu M. Methyl syringate, a low-molecular-weight phenolic ester, as an activator of the chemosensory ion channel TRPA1. Arch Pharm Res. 2012;35:2211-8 pubmed publisher
    ..4 ?M) and cinnamaldehyde (EC(50) = 22.2 ?M), the present study provides evidence that methyl syringate from K. pictus is a specific and selective activator of hTRPA1. ..
  4. Lennertz R, Kossyreva E, Smith A, Stucky C. TRPA1 mediates mechanical sensitization in nociceptors during inflammation. PLoS ONE. 2012;7:e43597 pubmed publisher
  5. Wang L, Cvetkov T, Chance M, Moiseenkova Bell V. Identification of in vivo disulfide conformation of TRPA1 ion channel. J Biol Chem. 2012;287:6169-76 pubmed publisher
    ..These results indicate that the activation mechanism of TRPA1 may involve N-terminal conformation changes and disulfide bonding between critical cysteine residues. ..
  6. Senthilan P, Piepenbrock D, Ovezmyradov G, Nadrowski B, Bechstedt S, Pauls S, et al. Drosophila auditory organ genes and genetic hearing defects. Cell. 2012;150:1042-54 pubmed publisher
    ..Our findings demonstrate mechanosensory roles for ionotropic receptors and visual rhodopsins and indicate that different sensory modalities utilize common signaling cascades. ..
  7. Huang D, Li S, Dhaka A, Story G, Cao Y. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura. Mol Pain. 2012;8:66 pubmed publisher
    ..These results provide an anatomical basis for understanding further the functional significance of TRP channels in headache pathophysiology. ..
  8. Shintaku K, Uchida K, Suzuki Y, Zhou Y, Fushiki T, Watanabe T, et al. Activation of transient receptor potential A1 by a non-pungent capsaicin-like compound, capsiate. Br J Pharmacol. 2012;165:1476-86 pubmed publisher
    ..Taken together, these results indicate that capsinoids activate TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in physiological phenomena associated with capsinoid treatment. ..
  9. Cordero Morales J, Gracheva E, Julius D. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc Natl Acad Sci U S A. 2011;108:E1184-91 pubmed publisher
    ..These findings provide a framework for understanding how restricted changes in TRPA1 sequence account for evolution of physiologically diverse channels, also identifying portable modules that specify thermosensitivity. ..

More Information


  1. García Añoveros J, Wiwatpanit T. TRPML2 and mucolipin evolution. Handb Exp Pharmacol. 2014;222:647-58 pubmed publisher
    ..Given the restricted expression of TRPML2 in immune cells, this evolutionary history suggests a functional role in the adaptive immunity characteristic of vertebrates. ..
  2. Numazawa S, Takase M, Ahiko T, Ishii M, Shimizu S, Yoshida T. Possible involvement of transient receptor potential channels in electrophile-induced insulin secretion from RINm5F cells. Biol Pharm Bull. 2012;35:346-54 pubmed
  3. Andrade E, Meotti F, Calixto J. TRPA1 antagonists as potential analgesic drugs. Pharmacol Ther. 2012;133:189-204 pubmed publisher
    ..We also discuss recent advances in the search for new analgesic medicines targeting the TRPA1 channel. ..
  4. Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S, De Siena G, et al. The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. Brain. 2012;135:376-90 pubmed publisher
  5. Yan Z, Zhang W, He Y, Gorczyca D, Xiang Y, Cheng L, et al. Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation. Nature. 2013;493:221-5 pubmed publisher
    ..Our study also suggests that different mechanosensitive channels may be used to sense gentle touch versus noxious mechanical stimuli. ..
  6. Mukhopadhyay I, Gomes P, Aranake S, Shetty M, Karnik P, Damle M, et al. Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res. 2011;31:350-8 pubmed publisher
  7. Shabir S, Cross W, Kirkwood L, Pearson J, Appleby P, Walker D, et al. Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium. Am J Physiol Renal Physiol. 2013;305:F396-406 pubmed publisher
    ..These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting...
  8. Wakabayashi K, Gustafson A, Sidransky E, Goldin E. Mucolipidosis type IV: an update. Mol Genet Metab. 2011;104:206-13 pubmed publisher
    ..An enhanced awareness of the manifestations of this disorder may help to elucidate the true frequency and range of symptoms associated with MLIV, providing insight into the pathogenesis of this multi-system disease...
  9. Cattaruzza F, Johnson C, Leggit A, Grady E, Schenk A, Cevikbas F, et al. Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice. Am J Physiol Gastrointest Liver Physiol. 2013;304:G1002-12 pubmed publisher
    ..We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain. ..
  10. Bautista D, Pellegrino M, Tsunozaki M. TRPA1: A gatekeeper for inflammation. Annu Rev Physiol. 2013;75:181-200 pubmed publisher
    ..This dual function of TRPA1 as a detector and instigator of inflammatory agents makes TRPA1 a gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract. ..
  11. Engel M, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipović M, et al. TRPA1 and substance P mediate colitis in mice. Gastroenterology. 2011;141:1346-58 pubmed publisher
    ..Neuroimmune interactions control intestinal inflammation. Activation and sensitization of TRPA1 and release of substance P induce and maintain colitis in mice. ..
  12. Kiselyov K, Colletti G, Terwilliger A, Ketchum K, Lyons C, Quinn J, et al. TRPML: transporters of metals in lysosomes essential for cell survival?. Cell Calcium. 2011;50:288-94 pubmed publisher
    ..Further, alterations in metal transport by the TRPMLs due to mutations or environmental factors may contribute to their role in the disease phenotype and cell death. ..
  13. Wang Y, Chang R, Allgood S, Silver W, Liman E. A TRPA1-dependent mechanism for the pungent sensation of weak acids. J Gen Physiol. 2011;137:493-505 pubmed publisher
    ..We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis...
  14. Nishida M, Sumita M, Kitajima N. [Function and role of transient receptor potential channels]. Clin Calcium. 2013;23:561-8 pubmed publisher
    ..Recently, selective inhibitors of TRPC channels have been continuously identified, anticipating the possibility of drug discovery targeting TRPC channels for the treatment of heart failure. ..
  15. Dasari S, Abramowitz J, Birnbaumer L, Gulledge A. Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?. Neuroreport. 2013;24:550-4 pubmed publisher
  16. Barabas M, Kossyreva E, Stucky C. TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons. PLoS ONE. 2012;7:e47988 pubmed publisher
    ..Thus, IB4 binding is a better indicator than neuropeptides for TRPA1 expression. ..
  17. Samie M, Wang X, Zhang X, Goschka A, Li X, Cheng X, et al. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev Cell. 2013;26:511-24 pubmed publisher
    ..Thus phagocytic ingestion of large particles activates a phosphoinositide- and Ca2+-dependent exocytosis pathway to provide membranes necessary for pseudopod extension, leading to clearance of senescent and apoptotic cells in vivo. ..
  18. Moilanen L, Laavola M, Kukkonen M, Korhonen R, Leppänen T, Hogestatt E, et al. TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse. Sci Rep. 2012;2:380 pubmed publisher
    ..This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation. ..
  19. Thilo F, Vorderwülbecke B, Marki A, Krueger K, Liu Y, Baumunk D, et al. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells. Hypertension. 2012;59:1232-40 pubmed publisher
  20. Vriens J, Owsianik G, Hofmann T, Philipp S, Stab J, Chen X, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. 2011;70:482-94 pubmed publisher
    ..These experiments reveal an unanticipated role for TRPM3 as a thermosensitive nociceptor channel implicated in the detection of noxious heat. ..
  21. Dhennin Duthille I, Gautier M, Faouzi M, Guilbert A, Brevet M, Vaudry D, et al. High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues: correlation with pathological parameters. Cell Physiol Biochem. 2011;28:813-22 pubmed publisher
    ..The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma. ..
  22. Prole D, Taylor C. Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites. PLoS ONE. 2011;6:e26218 pubmed publisher
    ..Differences between human and parasite Ca(2+) channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect. ..
  23. Pertovaara A, Koivisto A. TRPA1 ion channel in the spinal dorsal horn as a therapeutic target in central pain hypersensitivity and cutaneous neurogenic inflammation. Eur J Pharmacol. 2011;666:1-4 pubmed publisher
    ..Blockade of the spinal TRPA1 channel-mediated regulation of transmission may also attenuate cutaneous neurogenic inflammation...
  24. Lucaciu O, Connell G. Itch sensation through transient receptor potential channels: a systematic review and relevance to manual therapy. J Manipulative Physiol Ther. 2013;36:385-93 pubmed publisher
    ..Therefore, TRP channels could serve as important, complex clinical targets for manual therapists. ..
  25. Richter D, Katz B, Oberacker T, Tzarfaty V, Belusic G, Minke B, et al. Translocation of the Drosophila transient receptor potential-like (TRPL) channel requires both the N- and C-terminal regions together with sustained Ca2+ entry. J Biol Chem. 2011;286:34234-43 pubmed publisher
    ..These results indicate that motifs present at both the N and C termini as well as sustained Ca(2+) entry are required for proper channel translocation. ..
  26. Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y, et al. TRPA1 underlies a sensing mechanism for O2. Nat Chem Biol. 2011;7:701-11 pubmed publisher
    ..The results suggest a new O(2)-sensing mechanism mediated by TRPA1. ..
  27. Nassini R, Pedretti P, Moretto N, Fusi C, Carnini C, Facchinetti F, et al. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS ONE. 2012;7:e42454 pubmed publisher
    ..This finding suggests that non-neuronal TRPA1 in the airways is functional and potentially capable of contributing to inflammatory airway diseases. ..
  28. Belvisi M, Dubuis E, Birrell M. Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest. 2011;140:1040-1047 pubmed publisher
  29. Schwartz E, La J, Scheff N, Davis B, Albers K, Gebhart G. TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic inflammation and pain in chronic pancreatitis. J Neurosci. 2013;33:5603-11 pubmed publisher
  30. Nilius B, Appendino G, Owsianik G. The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch. 2012;464:425-58 pubmed publisher
    ..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. ..
  31. Wang H, Schupp M, Zurborg S, Heppenstall P. Residues in the pore region of Drosophila transient receptor potential A1 dictate sensitivity to thermal stimuli. J Physiol. 2013;591:185-201 pubmed publisher
    ..Our results reveal specific molecular requirements for thermal activation of TRPA1 and provide mechanistic insight into this process. ..
  32. Bianchi B, Zhang X, Reilly R, Kym P, Yao B, Chen J. Species comparison and pharmacological characterization of human, monkey, rat, and mouse TRPA1 channels. J Pharmacol Exp Ther. 2012;341:360-8 pubmed publisher
    ..Our findings reveal that TRPA1 function differs between primate and rodent species and suggest that rhesus monkey could serve as a surrogate species for humans in preclinical studies. ..
  33. Jang Y, Lee Y, Kim S, Yang Y, Jung J, Oh U. Quantitative analysis of TRP channel genes in mouse organs. Arch Pharm Res. 2012;35:1823-30 pubmed publisher
    ..In summary, the expression profile of TRP channels in major tissues provides insight to their physiological functions and therefore application to new drug development. ..
  34. Knowlton W, Daniels R, Palkar R, McCoy D, McKemy D. Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS ONE. 2011;6:e25894 pubmed publisher
    ..Thus PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo. ..
  35. Lehnert B, Baker A, Gaudry Q, Chiang A, Wilson R. Distinct roles of TRP channels in auditory transduction and amplification in Drosophila. Neuron. 2013;77:115-28 pubmed publisher
    ..Thus, transduction and active amplification are genetically separable processes in Drosophila hearing. ..
  36. Koivisto A. Sustained TRPA1 activation in vivo. Acta Physiol (Oxf). 2012;204:248-54 pubmed publisher
    ..Chronic pain can be understood as a false alarm evoked by sustained and increased levels of endogenous TRPA1 agonists in various pathophysiological conditions. ..
  37. Avelino A, Charrua A, Frias B, Cruz C, Boudes M, de Ridder D, et al. Transient receptor potential channels in bladder function. Acta Physiol (Oxf). 2013;207:110-22 pubmed publisher
    ..The therapeutic interest of modulating the activity of TRP channels to treat bladder dysfunctions is also discussed. ..
  38. Andersson D, Gentry C, Alenmyr L, Killander D, Lewis S, Andersson A, et al. TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid ?(9)-tetrahydrocannabiorcol. Nat Commun. 2011;2:551 pubmed publisher
    ..Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain...
  39. Materazzi S, Fusi C, Benemei S, Pedretti P, Patacchini R, Nilius B, et al. TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch. 2012;463:561-9 pubmed publisher
    ..Paclitaxel via oxygen radical formation targets TRPA1 and TRPV4, and both channels are key for the delayed development of mechanical allodynia. Cold allodynia is, however, entirely dependent on TRPA1. ..
  40. Komatsu T, Uchida K, Fujita F, Zhou Y, Tominaga M. Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner. Pflugers Arch. 2012;463:549-59 pubmed publisher
    ..We conclude that primary and secondary alcohols activate hTRPA1 in a carbon chain length-dependent manner. TRPA1 could be a sensor of alcohols inducing skin, eye and nasal irritation in human...
  41. Inoue N, Ito S, Nogawa M, Tajima K, Kyoi T. Etodolac blocks the allyl isothiocyanate-induced response in mouse sensory neurons by selective TRPA1 activation. Pharmacology. 2012;90:47-54 pubmed publisher
    ..Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain. ..
  42. Ogawa H, Takahashi K, Miura S, Imagawa T, Saito S, Tominaga M, et al. H(2)S functions as a nociceptive messenger through transient receptor potential ankyrin 1 (TRPA1) activation. Neuroscience. 2012;218:335-43 pubmed publisher
    ..These results suggest that H(2)S functions as a nociceptive messenger through the activation of TRPA1 channels. TRPA1 may be a therapeutic target for H(2)S-related algesic action, especially under inflammatory conditions...
  43. Shen D, Wang X, Li X, Zhang X, Yao Z, Dibble S, et al. Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release. Nat Commun. 2012;3:731 pubmed publisher
    ..We propose that abnormal accumulation of luminal lipids causes secondary lysosome storage by blocking TRPML1- and Ca(2+)-dependent lysosomal trafficking. ..
  44. Lev S, Katz B, Tzarfaty V, Minke B. Signal-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate without activation of phospholipase C: implications on gating of Drosophila TRPL (transient receptor potential-like) channel. J Biol Chem. 2012;287:1436-47 pubmed publisher
    ..This suggests that PI(4,5)P(2) is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. ..
  45. Chen J, Kang D, Xu J, Lake M, Hogan J, Sun C, et al. Species differences and molecular determinant of TRPA1 cold sensitivity. Nat Commun. 2013;4:2501 pubmed publisher
    ..This residue difference also underlies the species-specific effects of menthol. Together, our findings identify the species-specific cold activation of TRPA1 and reveal a molecular determinant of cold-sensitive gating. ..
  46. Nassini R, Gees M, Harrison S, De Siena G, Materazzi S, Moretto N, et al. Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain. 2011;152:1621-31 pubmed publisher
  47. Eijkelkamp N, Quick K, Wood J. Transient receptor potential channels and mechanosensation. Annu Rev Neurosci. 2013;36:519-46 pubmed publisher
    ..Here we overview recent advances in this rapidly expanding field, focusing on somatosensation, hearing, the cardiovascular system, and interactions between TRP channels and other proteins involved in mechanoelectrical signaling. ..
  48. Moran M, McAlexander M, Biro T, Szallasi A. Transient receptor potential channels as therapeutic targets. Nat Rev Drug Discov. 2011;10:601-20 pubmed publisher
    ..This Review focuses on recent developments in the TRP channel-related field, and highlights potential opportunities for therapeutic intervention. ..
  49. Grace M, Birrell M, Dubuis E, Maher S, Belvisi M. Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax. 2012;67:891-900 pubmed publisher
    ..However, how this occurs is not understood...
  50. Benini A, Bozzato A, Mantovanelli S, Calvarini L, Giacopuzzi E, Bresciani R, et al. Characterization and expression analysis of mcoln1.1 and mcoln1.2, the putative zebrafish co-orthologs of the gene responsible for human mucolipidosis type IV. Int J Dev Biol. 2013;57:85-93 pubmed publisher
    ..TRPML1 belongs to a transient receptor potential channels (TRP) subfamily, which in mammals includes two other members: mucolipin-2 (TRPML2) and mucolipin-3 ..
  51. Su Z, Anishkin A, Kung C, Saimi Y. The core domain as the force sensor of the yeast mechanosensitive TRP channel. J Gen Physiol. 2011;138:627-40 pubmed publisher
    ..Compared with the bacterial MscL, TRPY1 is much less sensitive to force, befitting a polymodal channel that relies on multiple stimuli. ..
  52. Trevisan G, Materazzi S, Fusi C, Altomare A, Aldini G, Lodovici M, et al. Novel therapeutic strategy to prevent chemotherapy-induced persistent sensory neuropathy by TRPA1 blockade. Cancer Res. 2013;73:3120-31 pubmed publisher
    ..Furthermore, they suggest prevention strategies for CIPN in patients through the use of early, short-term treatments with TRPA1 antagonists. ..
  53. Weng Y, Batista Schepman P, Barabas M, Harris E, Dinsmore T, Kossyreva E, et al. Prostaglandin metabolite induces inhibition of TRPA1 and channel-dependent nociception. Mol Pain. 2012;8:75 pubmed publisher
    ..Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics. ..