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Gene Review

TRPV1  -  transient receptor potential cation...

Homo sapiens

Synonyms: Capsaicin receptor, OTRPC1, Osm-9-like TRP channel 1, Transient receptor potential cation channel subfamily V member 1, TrpV1, ...
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Disease relevance of TRPV1

  • FINDINGS: In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers: in the mucosal layer, the median% area positive was 0.44 (range 0.30-0.59) in patients who were hypersensitive and 0.11 (0.00-0.21) in controls (p=0.0005) [1].
  • This process, called sensitization or hyperalgesia, is mediated by a variety of proinflammatory factors, including bradykinin, ATP and NGF, which cause sensitization to noxious heat stimuli by enhancing the membrane current carried by the heat- and capsaicin-gated ion channel, TRPV1 [2].
  • In primary dorsal root ganglion neurons, TRPV1 co-distributes in vesicles with Syt IX and the vesicular protein synaptobrevin [3].
  • Based on our data we propose a model of the TM3/4 region of TRPV1 bound to capsaicin or RTX that may aid in the development of potent TRPV1 antagonists with utility in the treatment of sensory disorders [4].
  • These findings strongly support TRPV1 as a significant novel player in human hair growth control, underscore the physiological importance of TRPV1 in human skin beyond nociception, and identify TRPV1 as a promising, novel target for pharmacological manipulations of epithelial growth disorders [5].

Psychiatry related information on TRPV1

  • As systemic administration of TRPV1 ligands reduces locomotor activity in normal rodents, we hypothesised that activation of TRPV1 by endocannabinoids could play a role in the control of voluntary movement and that such actions could be regulated by AMT and FAAH [6].
  • The translated gene shares 46% and 43% identity with VR1 and VRL-1, respectively, and maps to chromosome 12q23-24.1, a locus associated with bipolar affective disorder [7].
  • Invertebrate TRPV channels, five in Caenorhabditis elegans and two in Drosophila, have been shown to play a role in mechanosensation, such as hearing and proprioception in Drosophila and nose touch in C. elegans, and in the response to osmotic stimuli in C. elegans [8].
  • For both rVR1 and hVR1, time-response waveforms elicited by resiniferatoxin increased more gradually compared to other agonists [9].

High impact information on TRPV1

  • On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1 [10].
  • Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses [11].
  • Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin [11].
  • VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1 [11].
  • VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1 [11].

Chemical compound and disease context of TRPV1


Biological context of TRPV1

  • Phosphorylation of TRPV1 at a single tyrosine residue, Y200, followed by insertion of TRPV1 channels into the surface membrane, explains most of the rapid sensitizing actions of NGF [2].
  • In organ culture, TRPV1 activation by capsaicin resulted in a dose-dependent and TRPV1-specific inhibition of hair shaft elongation, suppression of proliferation, induction of apoptosis, premature HF regression (catagen), and up-regulation of intrafollicular transforming growth factor-beta(2) [5].
  • Therefore, our results indicate that PKC signaling promotes at least in part the SNARE-dependent exocytosis of TRPV1 to the cell surface [3].
  • High expression of TRPV1 has been detected in several inflammatory diseases of the colon and ileum, whereas neuropeptides released upon sensory nerve stimulation triggered by TRPV1 activation seem to play a role in intestinal motility disorders [17].
  • Thus, capsaicin interacted with TRPV1 expressed by BEAS-2B and other airway epithelial cells to cause the calcium-dependent production of cytokines and, conversely, calcium-independent cell death [18].

Anatomical context of TRPV1

  • Here, we show that intracellular Ca2+ mobilization via the purinergic receptor agonist ATP, the muscarinic receptor agonist carbachol or the Ca(2+)-ATPase inhibitor thapsigargin leads to formation of anandamide, and subsequent TRPV1-dependent Ca2+ influx in transfected cells and sensory neurons of rat dorsal root ganglia (DRG) [19].
  • Extracellular Ca2+-dependent desensitization of TRPV1 observed in patch-clamp experiments when using both heterologous expression systems and native sensory ganglia is thought to be one mechanism underlying the paradoxical effectiveness of capsaicin as an analgesic therapy [20].
  • TRPV1 was originally described on sensory neurons as a central integrator of various nociceptive stimuli [5].
  • In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes [21].
  • Noteworthily, we found that PKC activation induced a rapid delivery of functional TRPV1 channels to the plasma membrane [3].

Associations of TRPV1 with chemical compounds

  • The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively [22].
  • As yet, endogenously produced anandamide has not been shown to activate TRPV1, but this is of importance to understand the physiological function of this interaction [19].
  • Furthermore, these residues account for the reported pharmacological differences of RTX, PPAHV (phorbol 12-phenyl-acetate 13-acetate 20-homovanillate) and capsazepine between human and rat TRPV1 [4].
  • We found that forskolin, a stimulator of adenylate cyclase, decreased desensitization of TRPV1 [23].
  • We propose that residue Y671 is critical for the high relative Ca(2+) permeability of TRPV1 and participates in the structural rearrangements of the channel protein leading to Ca(2+)-dependent desensitization [24].

Physical interactions of TRPV1

  • ECaC constitutes the rate-limiting apical entry step in the process of active transcellular Ca(2+) transport and belongs to a superfamily of Ca(2+) channels that includes the vanilloid receptor and transient receptor potential channels [25].
  • Interestingly, TRPV1 binding was increased in the striatum of DAT KO mice, while CB1 receptor binding was unaffected [26].
  • Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated capsaicin responses [27].

Regulatory relationships of TRPV1


Other interactions of TRPV1

  • Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation [21].
  • With the exception of TRPV5 and TRPV6, TRPV channel subunits preferentially assemble into homomeric complexes [33].
  • The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively [34].
  • These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers [28].
  • In normal rats, the TRPV1 agonist capsaicin (1mg/kg) or the FAAH inhibitor URB597 (10mg/kg) caused a significant reduction in movement in both the horizontal (locomotion) and vertical (rearing) planes (-45% and -53% respectively with capsaicin; -33% and -37% for URB597) [6].

Analytical, diagnostic and therapeutic context of TRPV1


  1. Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency. Chan, C.L., Facer, P., Davis, J.B., Smith, G.D., Egerton, J., Bountra, C., Williams, N.S., Anand, P. Lancet (2003) [Pubmed]
  2. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. Zhang, X., Huang, J., McNaughton, P.A. EMBO J. (2005) [Pubmed]
  3. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. Morenilla-Palao, C., Planells-Cases, R., García-Sanz, N., Ferrer-Montiel, A. J. Biol. Chem. (2004) [Pubmed]
  4. Molecular determinants of vanilloid sensitivity in TRPV1. Gavva, N.R., Klionsky, L., Qu, Y., Shi, L., Tamir, R., Edenson, S., Zhang, T.J., Viswanadhan, V.N., Toth, A., Pearce, L.V., Vanderah, T.W., Porreca, F., Blumberg, P.M., Lile, J., Sun, Y., Wild, K., Louis, J.C., Treanor, J.J. J. Biol. Chem. (2004) [Pubmed]
  5. A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Bodó, E., Bíró, T., Telek, A., Czifra, G., Griger, Z., Tóth, B.I., Mescalchin, A., Ito, T., Bettermann, A., Kovács, L., Paus, R. Am. J. Pathol. (2005) [Pubmed]
  6. A role for vanilloid receptor 1 (TRPV1) and endocannabinnoid signalling in the regulation of spontaneous and L-DOPA induced locomotion in normal and reserpine-treated rats. Lee, J., Di Marzo, V., Brotchie, J.M. Neuropharmacology (2006) [Pubmed]
  7. Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Delany, N.S., Hurle, M., Facer, P., Alnadaf, T., Plumpton, C., Kinghorn, I., See, C.G., Costigan, M., Anand, P., Woolf, C.J., Crowther, D., Sanseau, P., Tate, S.N. Physiol. Genomics (2001) [Pubmed]
  8. Transient receptor potential vanilloid channels functioning in transduction of osmotic stimuli. Liedtke, W. J. Endocrinol. (2006) [Pubmed]
  9. Use of a fluorescent imaging plate reader--based calcium assay to assess pharmacological differences between the human and rat vanilloid receptor. Witte, D.G., Cassar, S.C., Masters, J.N., Esbenshade, T., Hancock, A.A. Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening. (2002) [Pubmed]
  10. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Xu, H., Ramsey, I.S., Kotecha, S.A., Moran, M.M., Chong, J.A., Lawson, D., Ge, P., Lilly, J., Silos-Santiago, I., Xie, Y., DiStefano, P.S., Curtis, R., Clapham, D.E. Nature (2002) [Pubmed]
  11. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Smith, G.D., Gunthorpe, M.J., Kelsell, R.E., Hayes, P.D., Reilly, P., Facer, P., Wright, J.E., Jerman, J.C., Walhin, J.P., Ooi, L., Egerton, J., Charles, K.J., Smart, D., Randall, A.D., Anand, P., Davis, J.B. Nature (2002) [Pubmed]
  12. 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]
  13. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Offertáler, L., Mo, F.M., Bátkai, S., Liu, J., Begg, M., Razdan, R.K., Martin, B.R., Bukoski, R.D., Kunos, G. Mol. Pharmacol. (2003) [Pubmed]
  14. Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1. Contassot, E., Wilmotte, R., Tenan, M., Belkouch, M.C., Schnüriger, V., de Tribolet, N., Burkhardt, K., Dietrich, P.Y., Bourkhardt, K. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  15. Transient Receptor Potential Vanilloid Subtype 1 Mediates Microglial Cell Death In Vivo and In Vitro via Ca2+-Mediated Mitochondrial Damage and Cytochrome c Release. Kim, S.R., Kim, S.U., Oh, U., Jin, B.K. J. Immunol. (2006) [Pubmed]
  16. Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons. Ohta, T., Ikemi, Y., Murakami, M., Imagawa, T., Otsuguro, K., Ito, S. J. Physiol. (Lond.) (2006) [Pubmed]
  17. Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. Geppetti, P., Trevisani, M. Br. J. Pharmacol. (2004) [Pubmed]
  18. Capsaicinoids cause inflammation and epithelial cell death through activation of vanilloid receptors. Reilly, C.A., Taylor, J.L., Lanza, D.L., Carr, B.A., Crouch, D.J., Yost, G.S. Toxicol. Sci. (2003) [Pubmed]
  19. Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels. van der Stelt, M., Trevisani, M., Vellani, V., De Petrocellis, L., Schiano Moriello, A., Campi, B., McNaughton, P., Geppetti, P., Di Marzo, V. EMBO J. (2005) [Pubmed]
  20. Structural determinant of TRPV1 desensitization interacts with calmodulin. Numazaki, M., Tominaga, T., Takeuchi, K., Murayama, N., Toyooka, H., Tominaga, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  21. 2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3. Hu, H.Z., Gu, Q., Wang, C., Colton, C.K., Tang, J., Kinoshita-Kawada, M., Lee, L.Y., Wood, J.D., Zhu, M.X. J. Biol. Chem. (2004) [Pubmed]
  22. 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]
  23. Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. Mohapatra, D.P., Nau, C. J. Biol. Chem. (2003) [Pubmed]
  24. A tyrosine residue in TM6 of the Vanilloid Receptor TRPV1 involved in desensitization and calcium permeability of capsaicin-activated currents. Mohapatra, D.P., Wang, S.Y., Wang, G.K., Nau, C. Mol. Cell. Neurosci. (2003) [Pubmed]
  25. Molecular mechanism of active Ca2+ reabsorption in the distal nephron. Hoenderop, J.G., Nilius, B., Bindels, R.J. Annu. Rev. Physiol. (2002) [Pubmed]
  26. Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Tzavara, E.T., Li, D.L., Moutsimilli, L., Bisogno, T., Di Marzo, V., Phebus, L.A., Nomikos, G.G., Giros, B. Biol. Psychiatry (2006) [Pubmed]
  27. The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Vetter, I., Wyse, B.D., Monteith, G.R., Roberts-Thomson, S.J., Cabot, P.J. Molecular pain [electronic resource] (2006) [Pubmed]
  28. Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. Gram, D.X., Ahrén, B., Nagy, I., Olsen, U.B., Brand, C.L., Sundler, F., Tabanera, R., Svendsen, O., Carr, R.D., Santha, P., Wierup, N., Hansen, A.J. Eur. J. Neurosci. (2007) [Pubmed]
  29. TRPM8 protein localization in trigeminal ganglion and taste papillae. Abe, J., Hosokawa, H., Okazawa, M., Kandachi, M., Sawada, Y., Yamanaka, K., Matsumura, K., Kobayashi, S. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  30. Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood. Saunders, C.I., Kunde, D.A., Crawford, A., Geraghty, D.P. Mol. Immunol. (2007) [Pubmed]
  31. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Watanabe, H., Vriens, J., Prenen, J., Droogmans, G., Voets, T., Nilius, B. Nature (2003) [Pubmed]
  32. 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]
  33. Homo- and heteromeric assembly of TRPV channel subunits. Hellwig, N., Albrecht, N., Harteneck, C., Schultz, G., Schaefer, M. J. Cell. Sci. (2005) [Pubmed]
  34. Potentiation of TRPV3 channel function by unsaturated fatty acids. Hu, H.Z., Xiao, R., Wang, C., Gao, N., Colton, C.K., Wood, J.D., Zhu, M.X. J. Cell. Physiol. (2006) [Pubmed]
  35. 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]
  36. Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons. Binzen, U., Greffrath, W., Hennessy, S., Bausen, M., Saaler-Reinhardt, S., Treede, R.D. Neuroscience (2006) [Pubmed]
  37. 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]
  38. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels. Groth, M., Helbig, T., Grau, V., Kummer, W., Haberberger, R.V. Respir. Res. (2006) [Pubmed]
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