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Gene Review

TRPA1  -  transient receptor potential cation...

Homo sapiens

Synonyms: ANKTM1, Ankyrin-like with transmembrane domains protein 1, FEPS, Transformation-sensitive protein p120, Transient receptor potential cation channel subfamily A member 1
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Disease relevance of TRPA1


High impact information on TRPA1


Biological context of TRPA1


Anatomical context of TRPA1

  • However, native neurones that appear to express TRPA1 respond very slowly to cold, and TRPA1 alone cannot account readily for cold nociceptor activity or cold pain in humans [9].
  • Allyl isothiocyanate, the pungent principle of wasabi and other mustard oils, produces pain by activating TRPA1, an excitatory ion channel on sensory nerve endings [6].
  • Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion [7].
  • Icilin, the peripheral cold channel agonist, activates TRPM8 and TRPA1, localized on dorsal root ganglia and trigeminal neurons in rats [10].
  • As shown here and previously, TRPA1 is expressed by hair cells as well as by most nociceptors (small neurons of dorsal root, trigeminal, and nodose ganglia) and localizes to their sensory terminals (mechanosensory stereocilia and peripheral free nerves, respectively) [11].

Associations of TRPA1 with chemical compounds

  • TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol [12].
  • Moreover, allicin and DADS activate the cloned TRPA1 channel when expressed in heterologous systems [13].
  • We identified by mass spectrometry fourteen cytosolic TRPA1 cysteines labelled by IA, three of which are required for normal channel function [14].
  • Finally, activation of TRPA1 by disulphide-bond-forming MTSEA is blocked by the reducing agent dithiothreitol (DTT) [14].
  • TRPV1 and ANKTM1 are mediating the pungency of nociceptor-specific chemicals such as capsaicin or mustard oil [15].

Regulatory relationships of TRPA1

  • We also confirm the importance of TRPA1 in WIN-induced dephosphorylation of TRPV1 in Chinese hamster ovary cells through targeted expression of one or both receptor channels [16].

Other interactions of TRPA1

  • Recently, novel TRP channels sensitive to low temperatures also have been cloned, namely, TRPM8 and TRPA1 [17].
  • Two heat sensitive channels, TRPV1 and TRPV4, and a cold-sensitive channel, TRPA1, were detected by RT-PCR [18].
  • TRPV2, TRPM8, and TRPA1 are also very likely to be involved in thermal nociception, because their activation thresholds are within the noxious range of temperatures [19].
  • Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs [20].
  • We describe that TRPA1 associates with the tumor-suppressor protein CYLD [8].

Analytical, diagnostic and therapeutic context of TRPA1


  1. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Bandell, M., Story, G.M., Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J., Patapoutian, A. Neuron (2004) [Pubmed]
  2. Induction of total insensitivity to capsaicin and hypersensitivity to garlic extract in human by decreased expression of TRPV1. Park, J.J., Lee, J., Kim, M.A., Back, S.K., Hong, S.K., Na, H.S. Neurosci. Lett. (2007) [Pubmed]
  3. TRPA1 Contributes to Cold, Mechanical, and Chemical Nociception but Is Not Essential for Hair-Cell Transduction. Kwan, K.Y., Allchorne, A.J., Vollrath, M.A., Christensen, A.P., Zhang, D.S., Woolf, C.J., Corey, D.P. Neuron (2006) [Pubmed]
  4. Outbreak caused by tobramycin-resistant Pseudomonas aeruginosa in a bone marrow transplantation unit. Lyytikäinen, O., Golovanova, V., Kolho, E., Ruutu, P., Sivonen, A., Tiittanen, L., Hakanen, M., Vuopio-Varkila, J. Scand. J. Infect. Dis. (2001) [Pubmed]
  5. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Bautista, D.M., Jordt, S.E., Nikai, T., Tsuruda, P.R., Read, A.J., Poblete, J., Yamoah, E.N., Basbaum, A.I., Julius, D. Cell (2006) [Pubmed]
  6. TRP channel activation by reversible covalent modification. Hinman, A., Chuang, H.H., Bautista, D.M., Julius, D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons. Mizushima, T., Obata, K., Katsura, H., Yamanaka, H., Kobayashi, K., Dai, Y., Fukuoka, T., Tokunaga, A., Mashimo, T., Noguchi, K. Neuroscience (2006) [Pubmed]
  8. TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD. Stokes, A., Wakano, C., Koblan-Huberson, M., Adra, C.N., Fleig, A., Turner, H. Cell. Signal. (2006) [Pubmed]
  9. ThermoTRP channels and cold sensing: what are they really up to? Reid, G. Pflugers Arch. (2005) [Pubmed]
  10. Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum of rats. Werkheiser, J.L., Rawls, S.M., Cowan, A. Amino Acids (2006) [Pubmed]
  11. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. Nagata, K., Duggan, A., Kumar, G., García-Añoveros, J. J. Neurosci. (2005) [Pubmed]
  12. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Namer, B., Seifert, F., Handwerker, H.O., Maihöfner, C. Neuroreport (2005) [Pubmed]
  13. Pungent products from garlic activate the sensory ion channel TRPA1. Bautista, D.M., Movahed, P., Hinman, A., Axelsson, H.E., Sterner, O., Högestätt, E.D., Julius, D., Jordt, S.E., Zygmunt, P.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Macpherson, L.J., Dubin, A.E., Evans, M.J., Marr, F., Schultz, P.G., Cravatt, B.F., Patapoutian, A. Nature (2007) [Pubmed]
  15. The role of TRP channels in sensory neurons. Koltzenburg, M. Novartis Found. Symp. (2004) [Pubmed]
  16. Cannabinoid WIN 55,212-2 Regulates TRPV1 Phosphorylation in Sensory Neurons. Jeske, N.A., Patwardhan, A.M., Gamper, N., Price, T.J., Akopian, A.N., Hargreaves, K.M. J. Biol. Chem. (2006) [Pubmed]
  17. Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions. Calixto, J.B., Kassuya, C.A., André, E., Ferreira, J. Pharmacol. Ther. (2005) [Pubmed]
  18. Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes. Kochukov, M.Y., McNearney, T.A., Fu, Y., Westlund, K.N. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  19. Thermosensation and pain. Tominaga, M., Caterina, M.J. J. Neurobiol. (2004) [Pubmed]
  20. More than cool: promiscuous relationships of menthol and other sensory compounds. Macpherson, L.J., Hwang, S.W., Miyamoto, T., Dubin, A.E., Patapoutian, A., Story, G.M. Mol. Cell. Neurosci. (2006) [Pubmed]
  21. Differential expression of capsaicin-, menthol-, and mustard oil-sensitive receptors in naive rat geniculate ganglion neurons. Katsura, H., Tsuzuki, K., Noguchi, K., Sakagami, M. Chem. Senses (2006) [Pubmed]
  22. TRPA1. Garc??a-A??overos, J., Nagata, K. Handbook of experimental pharmacology (2007) [Pubmed]
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