TRPV3

Last updated
TRPV3
7mij2.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TRPV3 , FNEPPK2, OLMS, VRL3, transient receptor potential cation channel subfamily V member 3, OLMS1
External IDs OMIM: 607066; MGI: 2181407; HomoloGene: 17040; GeneCards: TRPV3; OMA:TRPV3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

162514

246788

Ensembl

ENSG00000167723

ENSMUSG00000043029

UniProt

Q8NET8

Q8K424

RefSeq (mRNA)

NM_001258205
NM_145068

NM_145099
NM_001371006

RefSeq (protein)

NP_001245134
NP_659505

NP_659567
NP_001357935

Location (UCSC) Chr 17: 3.51 – 3.56 Mb Chr 11: 73.16 – 73.19 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transient receptor potential cation channel, subfamily V, member 3, also known as TRPV3, is a human gene encoding the protein of the same name.

Contents

The TRPV3 protein belongs to a family of nonselective cation channels that function in a variety of processes, including temperature sensation and vasoregulation. The thermosensitive members of this family are expressed in subsets of human sensory neurons that terminate in the skin, and are activated at distinct physiological temperatures. This channel is activated at temperatures between 22 and 40 degrees C. The gene lies in close proximity to another family member (TRPV1) gene on chromosome 17, and the two encoded proteins are thought to associate with each other to form heteromeric channels. [5]

Function

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. [6] Mice lacking these protein are unable to sense elevated temperatures (>33 °C) but are able to sense cold and noxious heat. [7] 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. [8] The role of TRPV3 channels in the brain is unclear, but appears to play a role in mood regulation. [9] The protective effects of the natural product, incensole acetate were partially mediated by TRPV3 channels. [10]

Modulation

The TRPV3 channel is directly activated by various natural compounds like carvacrol, thymol and eugenol. [11] Several other monoterpenoids which cause either feeling of warmth or are skin sensitizers can also open the channel. [12] Monoterpenoids also induce agonist-specific desensitization of TRPV3 channels in a calcium-independent manner. [13]

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. [14] [15] [16] [17] [18]

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. [19] Drofenine also acts as a TRPV3 agonist in addition to its other actions. [20] Conversely, icilin has been shown to act as a TRPV3 antagonist, as well as a TRPM8 agonist. [21] Forsythoside B acts as a TRPV3 inhibitor among other actions. [22] Farnesyl pyrophosphate is an endogenous agonist of TRPV3, [23] while incensole acetate from frankincense also acts as an agonist at TRPV3. [24] TRPV3-74a is a selective TRPV3 antagonist. [25]

Ligands

Agonists

See also

Related Research Articles

<span class="mw-page-title-main">Resolvin</span> Class of chemical compounds

Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as from two isomers of docosapentaenoic acid (DPA), one omega-3 and one omega-6 fatty acid. As autacoids similar to hormones acting on local tissues, resolvins are under preliminary research for their involvement in promoting restoration of normal cellular function following the inflammation that occurs after tissue injury. Resolvins belong to a class of polyunsaturated fatty acid (PUFA) metabolites termed specialized proresolving mediators (SPMs).

<span class="mw-page-title-main">WIN 55,212-2</span> Chemical compound

WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.

<span class="mw-page-title-main">TRPV1</span> Human protein for regulating body temperature

The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels. Fatty acid metabolites with affinity for this receptor are produced by cyanobacteria, which diverged from eukaryotes at least 2000 million years ago (MYA). The function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception). In primary afferent sensory neurons, it cooperates with TRPA1 to mediate the detection of noxious environmental stimuli.

<span class="mw-page-title-main">TRPV</span> Subgroup of TRP cation channels named after the vanilloid receptor

TRPV is a family of transient receptor potential cation channels in animals. All TRPVs are highly calcium selective.

Most of the eicosanoid receptors are integral membrane protein G protein-coupled receptors (GPCRs) that bind and respond to eicosanoid signaling molecules. Eicosanoids are rapidly metabolized to inactive products and therefore are short-lived. Accordingly, the eicosanoid-receptor interaction is typically limited to a local interaction: cells, upon stimulation, metabolize arachidonic acid to an eicosanoid which then binds cognate receptors on either its parent cell or on nearby cells to trigger functional responses within a restricted tissue area, e.g. an inflammatory response to an invading pathogen. In some cases, however, the synthesized eicosanoid travels through the blood to trigger systemic or coordinated tissue responses, e.g. prostaglandin (PG) E2 released locally travels to the hypothalamus to trigger a febrile reaction. An example of a non-GPCR receptor that binds many eicosanoids is the PPAR-γ nuclear receptor.

<span class="mw-page-title-main">TRPA1</span> Protein and coding gene in humans

Transient receptor potential cation channel, subfamily A, member 1, also known as transient receptor potential ankyrin 1, TRPA1, or The Wasabi Receptor, is a protein that in humans is encoded by the TRPA1 gene.

<span class="mw-page-title-main">TRPV4</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the TRPV4 gene.

<span class="mw-page-title-main">TRPM8</span> Protein-coding gene in humans

Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the TRPM8 gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors.

<span class="mw-page-title-main">Formyl peptide receptor 2</span> Protein-coding gene in the species Homo sapiens

N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. The human receptor protein is encoded by the FPR2 gene and is activated to regulate cell function by binding any one of a wide variety of ligands including not only certain N-Formylmethionine-containing oligopeptides such as N-Formylmethionine-leucyl-phenylalanine (FMLP) but also the polyunsaturated fatty acid metabolite of arachidonic acid, lipoxin A4 (LXA4). Because of its interaction with lipoxin A4, FPR2 is also commonly named the ALX/FPR2 or just ALX receptor.

<span class="mw-page-title-main">NAGly receptor</span> Protein-coding gene in the species Homo sapiens

N-Arachidonyl glycine receptor, also known as G protein-coupled receptor 18 (GPR18), is a protein that in humans is encoded by the GPR18 gene. Along with the other previously "orphan" receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors. It has been found to be involved in the regulation of intraocular pressure.

<span class="mw-page-title-main">GPR32</span> Human biochemical receptor

G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human receptor (biochemistry) belonging to the rhodopsin-like subfamily of G protein-coupled receptors.

<span class="mw-page-title-main">Iodoresiniferatoxin</span> Chemical compound

Iodoresiniferatoxin (I-RTX) is a strong competitive antagonist of the Transient Receptor Potential Vanilloid 1 (TRPV1) receptor. I-RTX is derived from resiniferatoxin (RTX).

Relief from chronic pain remains a recognized unmet medical need. Consequently, the search for new analgesic agents is being intensively studied by the pharmaceutical industry. The TRPV1 receptor is a ligand gated ion channel that has been implicated in mediation of many types of pain and therefore studied most extensively. The first competitive antagonist, capsazepine, was first described in 1990; since then, several TRPV1 antagonists have entered clinical trials as analgesic agents. Should these new chemical entities relieve symptoms of chronic pain, then this class of compounds may offer one of the first novel mechanisms for the treatment of pain in many years.

Zucapsaicin (Civanex) is a medication used to treat osteoarthritis of the knee and other neuropathic pain. Zucapsaicin is a member of phenols and a member of methoxybenzenes. It is a modulator of transient receptor potential cation channel subfamily V member 1 (TRPV-1), also known as the vanilloid or capsaicin receptor 1 that reduces pain, and improves articular functions. It is the cis-isomer of capsaicin. Civamide, manufactured by Winston Pharmaceuticals, is produced in formulations for oral, nasal, and topical use.

Specialized pro-resolving mediators are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of lipoxygenase, cyclooxygenase, and cytochrome P450 monooxygenase enzymes. Pre-clinical studies, primarily in animal models and human tissues, implicate SPM in orchestrating the resolution of inflammation. Prominent members include the resolvins and protectins.

<span class="mw-page-title-main">AMG-9810</span> Chemical compound

AMG-9810 is a drug which acts as a potent and selective antagonist for the TRPV1 receptor. It has analgesic and antiinflammatory effects and is used in scientific research, but has not been developed for medical use. It has high antagonist potency and good bioavailability and pharmacokinetics, and so has been used to study the role of TRPV1 in areas other than pain perception, such as its roles in the brain.

<span class="mw-page-title-main">HC-067047</span> Chemical compound

HC-067047 is a drug which acts as a potent and selective antagonist for the TRPV4 receptor. It has been used to investigate the role of TRPV4 receptors in a number of areas, such as regulation of blood pressure, bladder function and some forms of pain, as well as neurological functions.

<span class="mw-page-title-main">Forsythoside B</span> Chemical compound

Forsythoside B is a natural product from the phenylpropanoid/polyphenolic glycoside group, which is found in a number of plant species in the mint order such as Marrubium alysson, Phlomis armeniaca, Scutellaria salviifolia, Phlomoides tuberosa, Phlomoides rotata, Pedicularis longiflora and Teucrium chamaedrys, several of which are used in Chinese traditional medicine in preparations such as Shuanghuanglian (双黄连). It acts as an inhibitor of inflammatory mediators such as TNF-alpha, IL-6, IκB and NF-κB, as well as the temperature sensitive channel TRPV3, but also activates the RhoA/ROCK signaling pathway which can cause hypersensitivity reactions when it is injected intravenously.

<span class="mw-page-title-main">TRPV3-74a</span> Chemical compound

TRPV3-74a is a drug which acts as a selective antagonist for the TRPV3 calcium channel. It has analgesic effects in animal studies against both neuropathic pain and normal pain responses.

<span class="mw-page-title-main">AMG-517</span> Chemical compound

AMG-517 is a drug which acts as a potent and selective blocker of the TRPV1 ion channel. It was developed as a potential treatment for chronic pain, but while it was an effective analgesic in animal studies it was dropped from human clinical trials at Phase I due to producing hyperthermia as a side effect, as well as poor water solubility. It is still used in scientific research into the function of the TRPV1 channel and its role in pain and inflammation, and has been used as a template for the design of several newer analogues which have improved properties.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167723 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000043029 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: TRPV3 transient receptor potential cation channel, subfamily V, member 3".
  6. ↑ Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, et al. (June 2002). "A heat-sensitive TRP channel expressed in keratinocytes". Science. 296 (5575): 2046–9. Bibcode:2002Sci...296.2046P. doi:10.1126/science.1073140. PMID   12016205. S2CID   6180133.
  7. ↑ Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, et al. (March 2005). "Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin". Science. 307 (5714): 1468–72. Bibcode:2005Sci...307.1468M. doi:10.1126/science.1108609. PMID   15746429. S2CID   11504772.
  8. ↑ Imura K, Yoshioka T, Hikita I, Tsukahara K, Hirasawa T, Higashino K, et al. (November 2007). "Influence of TRPV3 mutation on hair growth cycle in mice". Biochemical and Biophysical Research Communications. 363 (3): 479–83. doi:10.1016/j.bbrc.2007.08.170. PMID   17888882.
  9. ↑ "Incense on the brain, by Ran Shapira, Haaretz". Haaretz.
  10. ↑ Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS (March 2012). "Protective effects of incensole acetate on cerebral ischemic injury". Brain Research. 1443: 89–97. doi:10.1016/j.brainres.2012.01.001. PMC   3294134 . PMID   22284622.
  11. ↑ Xu H, Delling M, Jun JC, Clapham DE (2006). "Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels". Nat. Neurosci. 9 (5): 628–35. doi:10.1038/nn1692. PMID   16617338. S2CID   13088422.
  12. ↑ Vogt-Eisele AK, Weber K, Sherkheli MA, et al. (2007). "Monoterpenoid agonists of TRPV3". Br. J. Pharmacol. 151 (4): 530–40. doi:10.1038/sj.bjp.0707245. PMC   2013969 . PMID   17420775.
  13. ↑ Sherkheli MA, et al. (2009). "Monoterpenoids Induce Agonist-Specific Desensitization of Transient Receptor Potential Vanilloid-3 (TRPV3) ion Channels". J Pharm Pharm Sci. 12 (1): 116–128. doi: 10.18433/j37c7k . PMID   19470296.
  14. ↑ Qu Q, Xuan W, Fan GH (2015). "Roles of resolvins in the resolution of acute inflammation". Cell Biology International. 39 (1): 3–22. doi:10.1002/cbin.10345. PMID   25052386. S2CID   10160642.
  15. ↑ Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMC   4315926 . PMID   25359497.
  16. ↑ Lim JY, Park CK, Hwang SW (2015). "Biological Roles of Resolvins and Related Substances in the Resolution of Pain". BioMed Research International. 2015: 830930. doi: 10.1155/2015/830930 . PMC   4538417 . PMID   26339646.
  17. ↑ Ji RR, Xu ZZ, Strichartz G, Serhan CN (2011). "Emerging roles of resolvins in the resolution of inflammation and pain". Trends in Neurosciences. 34 (11): 599–609. doi:10.1016/j.tins.2011.08.005. PMC   3200462 . PMID   21963090.
  18. ↑ Serhan CN, Chiang N, Dalli J (2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC   4515371 . PMID   25857211.
  19. ↑ Chung MK, Lee H, Mizuno A, Suzuki M, Caterina MJ (June 2004). "2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3". The Journal of Neuroscience. 24 (22): 5177–82. doi:10.1523/JNEUROSCI.0934-04.2004. PMC   6729202 . PMID   15175387.
  20. ↑ Deering-Rice CE, Mitchell VK, Romero EG, Abdel Aziz MH, Ryskamp DA, Križaj D, et al. (October 2014). "Drofenine: A 2-APB Analogue with Greater Selectivity for Human TRPV3". Pharmacology Research & Perspectives. 2 (5): e00062. doi:10.1002/prp2.62. PMC   4115637 . PMID   25089200.
  21. ↑ Sherkheli MA, Gisselmann G, Hatt H (2012). "Supercooling agent icilin blocks a warmth-sensing ion channel TRPV3". TheScientificWorldJournal. 2012: 982725. doi: 10.1100/2012/982725 . PMC   3324214 . PMID   22548000.
  22. ↑ Zhang H, Sun X, Qi H, Ma Q, Zhou Q, Wang W, Wang K (January 2019). "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". The Journal of Pharmacology and Experimental Therapeutics. 368 (1): 21–31. doi: 10.1124/jpet.118.254045 . PMID   30377214.
  23. ↑ Bang S, Yoo S, Yang TJ, Cho H, Hwang SW (June 2010). "Farnesyl pyrophosphate is a novel pain-producing molecule via specific activation of TRPV3". The Journal of Biological Chemistry. 285 (25): 19362–71. doi: 10.1074/jbc.M109.087742 . PMC   2885216 . PMID   20395302.
  24. ↑ Moussaieff A, Rimmerman N, Bregman T, Straiker A, Felder CC, Shoham S, et al. (August 2008). "Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain". FASEB Journal. 22 (8): 3024–34. doi: 10.1096/fj.07-101865 . PMC   2493463 . PMID   18492727.
  25. ↑ Gomtsyan A, Schmidt RG, Bayburt EK, Gfesser GA, Voight EA, Daanen JF, et al. (May 2016). "Synthesis and Pharmacology of (Pyridin-2-yl)methanol Derivatives as Novel and Selective Transient Receptor Potential Vanilloid 3 Antagonists". Journal of Medicinal Chemistry. 59 (10): 4926–47. doi:10.1021/acs.jmedchem.6b00287. PMID   27077528.

Further reading

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