TRPV3

The TRPV3 channel has wide tissue expression that is especially high in the skin (keratinocytes) but also in the brain. It functions as a molecular sensor for innocuous warm temperatures.{{cite journal | vauthors = Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian A | display-authors = 6 | title = A heat-sensitive TRP channel expressed in keratinocytes | journal = Science | volume = 296 | issue = 5575 | pages = 2046–9 | date = June 2002 | pmid = 12016205 | doi = 10.1126/science.1073140 | bibcode = 2002Sci...296.2046P | s2cid = 6180133 | url = https://hal.science/hal-00311330 }} Mice lacking these protein are unable to sense elevated temperatures (>33 °C) but are able to sense cold and noxious heat.{{cite journal | vauthors = Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A | display-authors = 6 | title = Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin | journal = Science | volume = 307 | issue = 5714 | pages = 1468–72 | date = March 2005 | pmid = 15746429 | doi = 10.1126/science.1108609 | bibcode = 2005Sci...307.1468M | s2cid = 11504772 | url = https://hal.science/hal-00118759 }} In addition to thermosensation TRPV3 channels seem to play a role in hair growth because mutations in the TRPV3 gene cause hair loss in mice.{{cite journal | vauthors = Imura K, Yoshioka T, Hikita I, Tsukahara K, Hirasawa T, Higashino K, Gahara Y, Arimura A, Sakata T | display-authors = 6 | title = Influence of TRPV3 mutation on hair growth cycle in mice | journal = Biochemical and Biophysical Research Communications | volume = 363 | issue = 3 | pages = 479–83 | date = November 2007 | pmid = 17888882 | doi = 10.1016/j.bbrc.2007.08.170 }} The role of TRPV3 channels in the brain is unclear, but appears to play a role in mood regulation.{{cite news | title = Incense on the brain, by Ran Shapira, Haaretz| newspaper = Haaretz| url = http://www.haaretz.com/print-edition/features/incense-on-the-brain-1.248292}} The protective effects of the natural product, incensole acetate were partially mediated by TRPV3 channels.{{cite journal | vauthors = Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS | title = Protective effects of incensole acetate on cerebral ischemic injury | journal = Brain Research | volume = 1443 | pages = 89–97 | date = March 2012 | pmid = 22284622 | pmc = 3294134 | doi = 10.1016/j.brainres.2012.01.001 }}

The TRPV3 channel is directly activated by various natural compounds like carvacrol, thymol and eugenol.{{cite journal |vauthors=Xu H, Delling M, Jun JC, Clapham DE |title=Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels |journal=Nat. Neurosci. |volume=9 |issue=5 |pages=628–35 |year=2006 |pmid=16617338 |doi=10.1038/nn1692 |s2cid=13088422 }} Several other monoterpenoids which cause either feeling of warmth or are skin sensitizers can also open the channel.{{cite journal |vauthors=Vogt-Eisele AK, Weber K, Sherkheli MA|title=Monoterpenoid agonists of TRPV3 |journal=Br. J. Pharmacol. |volume=151 |issue=4 |pages=530–40 |year=2007 |pmid=17420775 |doi=10.1038/sj.bjp.0707245 |pmc=2013969|display-authors=etal}} Monoterpenoids also induce agonist-specific desensitization of TRPV3 channels in a calcium-independent manner.{{cite journal | vauthors = Sherkheli MA et al | year = 2009 | title = Monoterpenoids Induce Agonist-Specific Desensitization of Transient Receptor Potential Vanilloid-3 (TRPV3) ion Channels | journal = J Pharm Pharm Sci | volume = 12 | issue = 1| pages = 116–128 | doi=10.18433/j37c7k| pmid = 19470296 | doi-access = free }}

Resolvin E1 (RvE1), RvD2, and 17R-RvD1 (see resolvins) are metabolites of the omega 3 fatty acids, eicosapentaenoic acid (for RvE1) or docosahexaenoic acid (for RvD2 and 17R-RvD1). These metabolites are members of the specialized proresolving mediators (SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. These SPMs also dampen pain perception arising from various inflammation-based causes in animal models. The mechanism behind their pain-dampening effects involves the inhibition of TRPV3, probably (in at least certain cases) by an indirect effect wherein they activate other receptors located on neurons or nearby microglia or astrocytes. CMKLR1, GPR32, FPR2, and NMDA receptors have been proposed to be the receptors through which these SPMs operate to down-regulate TRPV3 and thereby pain perception.{{cite journal | vauthors = Qu Q, Xuan W, Fan GH | title = Roles of resolvins in the resolution of acute inflammation | journal = Cell Biology International | volume = 39 | issue = 1 | pages = 3–22 | year = 2015 | pmid = 25052386 | doi = 10.1002/cbin.10345 | s2cid = 10160642 }}{{cite journal | vauthors = Serhan CN, Chiang N, Dalli J, Levy BD | title = Lipid mediators in the resolution of inflammation | journal = Cold Spring Harbor Perspectives in Biology | volume = 7 | issue = 2 | pages = a016311 | year = 2015 | pmid = 25359497 | doi = 10.1101/cshperspect.a016311 | pmc=4315926}}{{cite journal | vauthors = Lim JY, Park CK, Hwang SW | title = Biological Roles of Resolvins and Related Substances in the Resolution of Pain | journal = BioMed Research International | volume = 2015 | pages = 830930 | year = 2015 | pmid = 26339646 | pmc = 4538417 | doi = 10.1155/2015/830930 | doi-access = free }}{{cite journal | vauthors = Ji RR, Xu ZZ, Strichartz G, Serhan CN | title = Emerging roles of resolvins in the resolution of inflammation and pain | journal = Trends in Neurosciences | volume = 34 | issue = 11 | pages = 599–609 | year = 2011 | pmid = 21963090 | pmc = 3200462 | doi = 10.1016/j.tins.2011.08.005 }}{{cite journal | vauthors = Serhan CN, Chiang N, Dalli J | title = The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution | journal = Seminars in Immunology | volume = 27 | issue = 3 | pages = 200–15 | year = 2015 | pmid = 25857211 | pmc = 4515371 | doi = 10.1016/j.smim.2015.03.004 }}

2-Aminoethoxydiphenyl borate (2-APB) is a mixed agonist-antagonist of the TRPV3 receptor, acting as an antagonist at low concentrations but showing agonist activity when used in larger amounts.{{cite journal | vauthors = Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ | title = 2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3 | journal = The Journal of Neuroscience | volume = 24 | issue = 22 | pages = 5177–82 | date = June 2004 | pmid = 15175387 | doi = 10.1523/JNEUROSCI.0934-04.2004 | pmc = 6729202 }} Drofenine also acts as a TRPV3 agonist in addition to its other actions.{{cite journal | vauthors = Deering-Rice CE, Mitchell VK, Romero EG, Abdel Aziz MH, Ryskamp DA, Križaj D, Gopal VR, Reilly CA | display-authors = 6 | title = Drofenine: A 2-APB Analogue with Greater Selectivity for Human TRPV3 | journal = Pharmacology Research & Perspectives | volume = 2 | issue = 5 | pages = e00062 | date = October 2014 | pmid = 25089200 | doi = 10.1002/prp2.62 | pmc = 4115637 }} Conversely, icilin has been shown to act as a TRPV3 antagonist, as well as a TRPM8 agonist.{{cite journal | vauthors = Sherkheli MA, Gisselmann G, Hatt H | title = Supercooling agent icilin blocks a warmth-sensing ion channel TRPV3 | journal = TheScientificWorldJournal | year = 2012 | volume = 2012 | pages = 982725 | pmid = 22548000 | doi = 10.1100/2012/982725 | pmc = 3324214 | doi-access = free }} Forsythoside B acts as a TRPV3 inhibitor among other actions.{{cite journal | vauthors = Zhang H, Sun X, Qi H, Ma Q, Zhou Q, Wang W, Wang K | title = Pharmacological Inhibition of the Temperature-Sensitive and Ca2+-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel by Natural Forsythoside B Attenuates Pruritus and Cytotoxicity of Keratinocytes | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 368 | issue = 1 | pages = 21–31 | date = January 2019 | pmid = 30377214 | doi = 10.1124/jpet.118.254045 | doi-access = free }} Farnesyl pyrophosphate is an endogenous agonist of TRPV3,{{cite journal | vauthors = Bang S, Yoo S, Yang TJ, Cho H, Hwang SW | title = Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3 | journal = The Journal of Biological Chemistry | volume = 285 | issue = 25 | pages = 19362–71 | date = June 2010 | pmid = 20395302 | doi = 10.1074/jbc.M109.087742 | pmc = 2885216 | doi-access = free }} while incensole acetate from frankincense also acts as an agonist at TRPV3.{{cite journal | vauthors = Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, Kashman Y, Huang SM, Lee H, Shohami E, Mackie K, Caterina MJ, Walker JM, Fride E, Mechoulam R | display-authors = 6 | title = Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain | journal = FASEB Journal | volume = 22 | issue = 8 | pages = 3024–34 | date = August 2008 | pmid = 18492727 | pmc = 2493463 | doi = 10.1096/fj.07-101865 | doi-access = free }} TRPV3-74a is a selective TRPV3 antagonist.{{cite journal | vauthors = Gomtsyan A, Schmidt RG, Bayburt EK, Gfesser GA, Voight EA, Daanen JF, Schmidt DL, Cowart MD, Liu H, Altenbach RJ, Kort ME, Clapham B, Cox PB, Shrestha A, Henry R, Whittern DN, Reilly RM, Puttfarcken PS, Brederson JD, Song P, Li B, Huang SM, McDonald HA, Neelands TR, McGaraughty SP, Gauvin DM, Joshi SK, Banfor PN, Segreti JA, Shebley M, Faltynek CR, Dart MJ, Kym PR | display-authors = 6 | title = Synthesis and Pharmacology of (Pyridin-2-yl)methanol Derivatives as Novel and Selective Transient Receptor Potential Vanilloid 3 Antagonists | journal = Journal of Medicinal Chemistry | volume = 59 | issue = 10 | pages = 4926–47 | date = May 2016 | pmid = 27077528 | doi = 10.1021/acs.jmedchem.6b00287 }}

• Cannabidiol
• Tetrahydrocannabivarin
• Cannabigerolic acid
• Cannabigerovarin

• TRPV
• Endocannabinoid system

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• {{cite book | last = Islam | first = Md. Shahidul | name-list-style = vanc | title = Transient Receptor Potential Channels |date=January 2011 | volume = 704 | publisher = Springer | location = Berlin | pages = 700 | series = Advances in Experimental Medicine and Biology | isbn = 978-94-007-0264-6 }}
• {{cite journal | vauthors=Clapham DE, Julius D, Montell C, Schultz G |title=International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. |journal=Pharmacol. Rev. |volume=57 |issue= 4 |pages= 427–50 |year= 2006 |pmid= 16382100 |doi= 10.1124/pr.57.4.6 |s2cid=17936350 }}

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• {{MeshName|TRPV3+protein,+human}}

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{{Ion channels|g4}}

{{Transient receptor potential channel modulators}}

Category:Ion channels