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07-SEPTEMBER-2008 03:17:44 - TRPV1 transient receptor potential cation channel, subfamily V, member 1 Homo sapiens Identifiers Symbols TRPV1; DKFZp434K0220; VR1 External IDs OMIM: 602076 MGI: 1341787 HomoloGene: 12920 Gene ontology Molecular function: receptor activity ion channel activity calcium channel activity calcium ion binding calmodulin binding cation transmembrane transporter activity Cellular component: integral to plasma membrane membrane integral to membrane Biological process: thermoregulation ion transport calcium ion transport cell surface receptor linked signal transduction chemosensory behavior response to pH response to heat sensory perception of pain thermoception RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 7442 193034 Ensembl ENSG00000196689 ENSMUSG00000005952 Uniprot Q8NER1 Q3V318 Refseq NM_018727 mRNA NP_061197 protein NM_001001445 mRNA NP_001001445 protein Location Chr 17: 3.42 - 3.45 Mb Chr 11: 73.05 - 73.08 Mb Pubmed search 1 2 The Transient receptor potential vanilloid 1 or TRPV1 can refer to the TRP cation channel receptor or the gene which encodes it in Homo sapiens. TRPV1 is a nonselective ligand-gated cation channel that may be activated by a wide variety of exogenous and endogenous stimuli, including heat greater than 43°C, low pH, anandamide, N-arachidonoyl-dopamine, and capsaicin. TRPV1 receptors are found in the central nervous system and the peripheral nervous system and are involved in the transmission and modulation of pain, as well as the integration of diverse painful stimuli.12 Contents 1 Clinical significance 1.1 Peripheral nervous system 1.2 Central nervous system 2 See also 3 References 4 Further reading 5 External links Clinical significance TRPV1 blockade in vivo elicited hyperthermia in multiple species, from rodents to humans, suggesting that TRPV1 is involved in body temperature maintenance.3 Recently, AMG 517, a highly selective TRPV1 antagonist was dropped out of clinical trials due to the undesirable magnitude of hyperthermia.4 A second molecule, SB-705498 was also evaluated in the clinic but its effect on body temperature was not reported.5 Peripheral nervous system TRPV1 antagonists have shown efficacy in reducing nociception from inflammatory and neuropathic pain models in rats.6 This provides evidence that TRPV1 is the capsaicin's sole receptor.7 In humans, drugs acting at TRPV1 receptors could potentially be used to treat neuropathic pain associated with multiple sclerosis, chemotherapy, or amputation, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis.8 The role of TRPV1 in the regulation of body temperature has emerged in last few years. Based on a number of TRPV1 selective antagonists causing an increase in body temperature hyperthermia, it was proposed that TRPV1 is tonically active in vivo and regulates body temperature.3 In a recent report, it was found that tonically active TRPV1 channels are present in the viscera and keep an ongoing suppressive effect on body temperature.9 Central nervous system TRPV1 is also expressed at high levels in the central nervous system and has been proposed as a target for treatment of not only pain but also for other conditions such as anxiety.10 Furthermore TRPV1 appears to mediate long term depression LTD in the hippocampus.11 LTD has been linked to a decrease in the ability to make new memories, unlike its opposite long term potentiation LTP, which aids in memory formation. A dynamic pattern of LTD and LTP occuring at many synapses provides a code for memory formation. Long-term depression and subsequent prunning of dampened down synapses is important in memory formation. In rat brain slices, activation of TRV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD.11 Hence there may be therapeutic potential in antagonizing TRPV1 in the central nervous system, perhaps as a treatment for epilepsy TRPV1 is already a target in the peripheral nervous system for pain relief. See also Capsaicin Vanilloid Cannabinoid receptor References ^ Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, Marsh K, Bianchi B, McDonald H, Niforatos W, Neelands TR, Moreland RB, Decker MW, Lee CH, Sullivan JP, Faltynek CR 2006. TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J. Neurosci. 26 37: 9385-93. doi:10.1523/JNEUROSCI.1246-06.2006. PMID 16971522. ^ Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V 2002. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc. Natl. Acad. Sci. U.S.A. 99 12: 8400-5. doi:10.1073/pnas.122196999. PMID 12060783. ^ a b Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC March 2007. The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation. J. Neurosci. 27 13: 3366-74. doi:10.1523/JNEUROSCI.4833-06.2007. PMID 17392452. ^ Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Alvarez F, Bak A, Darling M, Gore A, Jang GR, Kesslak JP, Ni L, Norman MH, Palluconi G, Rose MJ, Salfi M, Tan E, Romanovsky AA, Banfield C, Davar G May 2008. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136 1-2: 202-10. doi:10.1016/j.pain.2008.01.024. PMID 18337008. ^ Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM November 2007. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain 132 1-2: 132-41. doi:10.1016/j.pain.2007.06.006. PMID 17659837. ^ Jhaveri MD, Elmes SJ, Kendall DA, Chapman V 2005. Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats. Eur. J. Neurosci. 22 2: 361-70. doi:10.1111/j.1460-9568.2005.04227.x. PMID 16045489. ^ Story GM, Crus-Orengo L 2008. Feel the Burn. American Scientist 95 4: 326-333. ISSN 0003-0996. ^ Gunthorpe MJ, Szallasi A 2008. Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms. Curr. Pharm. Des. 14 1: 32-41. PMID 18220816. ^ Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL, Bannon AW, Norman MH, Louis JC, Treanor JJ, Gavva NR, Romanovsky AA July 2007. Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J. Neurosci. 27 28: 7459-68. doi:10.1523/JNEUROSCI.1483-07.2007. PMID 17626206. ^ Starowicz K, Cristino L, Di Marzo V 2008. TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications. Curr. Pharm. Des. 14 1: 42-54. PMID 18220817. ^ a b Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA 2008. TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons. Neuron 57 5: 746-59. doi:10.1016/j.neuron.2007.12.027. PMID 18341994. Further reading Immke DC, Gavva NR October 2006. The TRPV1 receptor and nociception. Semin. Cell Dev. Biol. 17 5: 582-91. doi:10.1016/j.semcdb.2006.09.004. PMID 17196854. Heiner I, Eisfeld J, Lückhoff A 2004. Role and regulation of TRP channels in neutrophil granulocytes.. Cell Calcium 33 5-6: 533-40. PMID 12765698. Geppetti P, Trevisani M 2004. Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function.. Br. J. Pharmacol. 141 8: 1313-20. doi:10.1038/sj.bjp.0705768. PMID 15051629. Clapham DE, Julius D, Montell C, Schultz G 2006. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels.. Pharmacol. Rev. 57 4: 427-50. doi:10.1124/pr.57.4.6. PMID 16382100. Szallasi A, Cruz F, Geppetti P 2007. TRPV1: a therapeutic target for novel analgesic drugs?. Trends in molecular medicine 12 11: 545-54. doi:10.1016/j.molmed.2006.09.001. PMID 16996800. Pingle SC, Matta JA, Ahern GP 2007. Capsaicin receptor: TRPV1 a promiscuous TRP channel.. Handb Exp Pharmacol 179: 155-71. doi:10.1007/978-3-540-34891-7_9. PMID 17217056. Liddle RA 2007. The role of Transient Receptor Potential Vanilloid 1 TRPV1 channels in pancreatitis.. Biochim. Biophys. Acta 1772 8: 869-78. doi:10.1016/j.bbadis.2007.02.012. PMID 17428642. External links MeSH Vanilloid+receptors v d e Membrane transport protein: ion channels Ca2+: Calcium channel Voltage-gated L-type/Cavα 1.1, 1.2, 1.3, 1.4 N-type/Cavα2.2 P-type/Cavα2.1 Q-type/Cavα2.1 R-type/Cavα2.3 T-type/Cavα3.2 α2δ-subunits 1, 2 β-subunits β1, β2, β3, β4 γ-subunits γ1, γ2, γ3, γ4 Other Cation channels of sperm Inositol triphosphate receptor 1, 2, 3 Ryanodine receptor 1, 2, 3 Two-pore channel 1, 2 Na+: Sodium channel Voltage-gated Navα 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 7A Navβ 1, 2, 3, 4 Other Epithelial sodium channel α, β, γ, δ K+: Potassium channel Voltage-gated Kvα 1-6 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.10, 2.1, 2.2, 3.1, 3.2, 3.3, 3.4, 4.1, 4.2, 4.3, 5.1, 6.1, 6.2, 6.3, 6.4 Kvα 7-12 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 9.1, 9.2, 9.3, 10.1, 10.2, 11.1/hERG, 11.2, 11.3, 12.1, 12.2, 12.3 Kvβ 1, 2, 3 KCNIP 1, 2, 3, 4 minK/ISK MiRP 1, 2, 3 Shaker gene Inward-rectifier Kir 1.1, 2.1, 2.2, 2.3, 2.4 GIRK/Kir 3.1, 3.2, 3.3, 3.4 Kir 4.1, 4.2, 5.1, 6.1, 6.2, 7.1 Tandem pore domain K2P 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, 16, 17, 18 M+: TRP cation channel TRPA 1 TRPC 1, 2, 3, 4, 4AP, 5, 6, 7 TRPM 1, 2, 3, 4, 5, 6, 7, 8 TRPML 1, 2, 3 TRPP 1, 2 TRPV 1, 2, 3, 4, 5, 6 Cl-: Chloride channel CFTR CLCA 1, 2, 3, 4 CLCN 1, 2, 3, 4, 5, 6, 7, KA, KB CLIC 1, 2, 3, 4, 5, 6 CLNS 1A, 1B Cyclic nucleotide-gated α1, α2, α3, α4, β1, β3, H1, H2, H3, H4 Porin Aquaporin 1, 2, 3, 4, 5, 7, 8, 9 Voltage-dependent anion channel 1, 2, 3 Other/general Ligand-gated ion channel Voltage-gated ion channel Stretch-activated ion channel Retrieved from http://en..org/wiki/TRPV1 Categories: Genes on chromosome 17 | Human proteins | Ion channelsHidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 8 July 2008, at 18:04
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