8x94

Structural highlights

Function

TRPV1_HUMAN Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis.[UniProtKB:O35433]^{[1] [2] [3] [4]}

References

1. ↑ Hayes P, Meadows HJ, Gunthorpe MJ, Harries MH, Duckworth DM, Cairns W, Harrison DC, Clarke CE, Ellington K, Prinjha RK, Barton AJ, Medhurst AD, Smith GD, Topp S, Murdock P, Sanger GJ, Terrett J, Jenkins O, Benham CD, Randall AD, Gloger IS, Davis JB. Cloning and functional expression of a human orthologue of rat vanilloid receptor-1. Pain. 2000 Nov;88(2):205-15. doi: 10.1016/s0304-3959(00)00353-5. PMID:11050376 doi:http://dx.doi.org/10.1016/s0304-3959(00)00353-5
2. ↑ McIntyre P, McLatchie LM, Chambers A, Phillips E, Clarke M, Savidge J, Toms C, Peacock M, Shah K, Winter J, Weerasakera N, Webb M, Rang HP, Bevan S, James IF. Pharmacological differences between the human and rat vanilloid receptor 1 (VR1). Br J Pharmacol. 2001 Mar;132(5):1084-94. doi: 10.1038/sj.bjp.0703918. PMID:11226139 doi:http://dx.doi.org/10.1038/sj.bjp.0703918
3. ↑ Cortright DN, Crandall M, Sanchez JF, Zou T, Krause JE, White G. The tissue distribution and functional characterization of human VR1. Biochem Biophys Res Commun. 2001 Mar;281(5):1183-9. PMID:11243859 doi:http://dx.doi.org/10.1006/bbrc.2001.4482
4. ↑ Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, Wright JE, Jerman JC, Walhin JP, Ooi L, Egerton J, Charles KJ, Smart D, Randall AD, Anand P, Davis JB. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature. 2002 Jul 11;418(6894):186-90. doi: 10.1038/nature00894. Epub 2002 Jun 23. PMID:12077606 doi:http://dx.doi.org/10.1038/nature00894