# TRPV

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Subgroup of TRP cation channels named after the vanilloid receptor

Protein family

Transient receptor potential (TRP) ion channel Homology model of the TRPV1 ion channel tetramer (where the monomers are individually colored cyan, green, blue, and magenta respective) imbedded in a cartoon representation of a lipid bilayer. PIP2 signaling ligands are represented by space-filling models (carbon = white, oxygen = red, phosphorus = orange).[1] Identifiers Symbol TRP Pfam PF06011 InterPro IPR010308 Available protein structures: PDB IPR010308 PF06011 (ECOD; PDBsum) AlphaFold IPR010308 PF06011

**TRPV** is a family of [transient receptor potential](/source/Transient_receptor_potential_channel) [cation channels](/source/Ion_channel) (TRP channels) in animals. All TRPVs are highly calcium selective.

TRP channels are a large group of [ion channels](/source/Ion_channel) consisting of six protein families, located mostly on the [plasma membrane](/source/Plasma_membrane) of numerous human and animal cell types, and in some fungi.[2] TRP channels were initially discovered in the *trp* mutant strain of the fruit fly *[Drosophila](/source/Drosophila)* [3] that displayed transient elevation of potential in response to light stimuli, and were therefore named "transient receptor potential" channels.[4] The name now refers only to a family of proteins with similar structure and function, not to the mechanism of their activation. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. There are about 28 TRP channels that share some structural similarity to each other.[5] These are grouped into two broad groups: group 1 includes [TRPC](/source/TRPC) ( "C" for canonical), **TRPV** ("V" for [vanilloid](/source/Vanilloid)), [TRPM](/source/TRPM) ("M" for melastatin), [TRPN](/source/TRPN) and [TRPA](/source/TRPA_(channel)). In group 2 there are [TRPP](/source/TRPP) ("P" for polycystic) and [TRPML](/source/TRPML) ("ML" for mucolipin).

## Structure

Functional TRPV ion channels are [tetrameric](/source/Tetrameric_protein) in structure and are either homo-tetrameric (four identical subunits) or hetero-tetrameric (a total of four subunits selected from two or more types of subunits). The four subunits are symmetrically arranged around the ion conduction pore. Although the extent of heteromerization has been the subject of some debate, the most recent research in this area suggest that all four thermosensitive TRPVs (1-4) can form heteromers with each other. This result is in line with the general observation that TRP coassembly tends to occur between subunits with high sequence similarities. How TRP subunits recognize and interact with each other is still poorly understood.[6][7]

The TRPV channel [monomeric](/source/Monomer) subunit components each contain six [transmembrane](/source/Transmembrane) (TM) [domains](/source/Protein_domain) (designated S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segments.[8] TRPV subunits contain three to five [N-terminal](/source/N-terminus) [ankyrin repeats](/source/Ankyrin_repeats).[9]

## Function

TRPV proteins respond to the taste of garlic ([allicin](/source/Allicin)). [TRPV1](/source/TRPV1) contributes to heat and inflammation sensations and mediates the [pungency](/source/Pungency) and pain sensation associated with [capsaicin](/source/Capsaicin) and [piperine](/source/Piperine).

## Family members

The table below summarizes the functions and properties of the individual TRPV channel family members:[10][11]

group channel function tissue distribution Ca2+/Na+ selectivity heteromeric associated subunits other associated proteins 1 TRPV1 vanilloid (capsaicin) receptor and noxious thermosensor (43 °C) CNS and PNS 9:1 TRPV2, TRPV3 calmodulin, PI3 kinase TRPV2 osmo- and noxious heat thermosensor (52 °C) CNS, spleen and lung 3:1 TRPV1 TRPV3 warmth sensor channel (33-39 °C) Skin, CNS and PNS 12:1 TRPV1 TRPV4 osmo- and warmth sensor channel (27-34 °C) CNS and internal organs; human sperm[12] 6:1 aquaporin 5, calmodulin, pacsin 3 2 TRPV5 calcium-selective TRP channel intestine, kidney, placenta 100:1 TRPV6 annexin II / S100A10, calmodulin TRPV6 calcium-selective TRP channel kidney, intestine 130:1 TRPV5 annexin II / S100A10, calmodulin

## Clinical significance

Mutations in TRPs have been linked to [neurodegenerative](/source/Neurodegeneration) disorders, skeletal [dysplasia](/source/Dysplasia), kidney disorders,[2] and may play an important role in cancer. TRPs may make important therapeutic targets. There is significant clinical significance to TRPV1, TRPV2, and TRPV3's role as thermoreceptors, and TRPV4's role as mechanoreceptors; reduction of chronic pain may be possible by targeting ion channels involved in thermal, chemical, and mechanical sensation to reduce their sensitivity to stimuli.[13] For instance, the use of TRPV1 agonists would potentially inhibit [nociception](/source/Nociception) at TRPV1, particularly in pancreatic tissue where TRPV1 is highly expressed.[14] The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain.[2] TRPV1 antagonists inhibit nociception at TRPV1.

## Role in cancer

Altered expression of TRP proteins often leads to [tumorigenesis](/source/Tumorigenesis), clearly seen in TRPM1.[14] Particularly high levels of TRPV6 in prostate cancer have been noted. Such observations could be helpful in following cancer progression and could lead to the development of drugs over activating ion channels, leading to [apoptosis](/source/Apoptosis) and [necrosis](/source/Necrosis). Much research remains to be done as to whether TRP channel mutations lead to cancer progression or whether they are associated mutations.

## As drug targets

Four TRPVs (TRPV1, TRPV2, TRPV3, and TRPV4) are expressed in [afferent](/source/Afferent_nerve) [nociceptors](/source/Nociceptor), pain sensing neurons, where they act as transducers of thermal and chemical stimuli. Agonists, antagonists, or modulators of these channels may find application for the prevention and treatment of pain.[15] A number of TRPV1 selective [agonists](/source/Agonist) and [antagonists](/source/Receptor_antagonist) such as [resiniferatoxin](/source/Resiniferatoxin) were in [clinical trials](/source/Clinical_trial) for the treatment of various types of pain.[16]

## See also

- [Discovery and development of TRPV1 antagonists](/source/Discovery_and_development_of_TRPV1_antagonists)

- [TRPA1](/source/TRPA1)

## References

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1. **[^](#cite_ref-pmid9535843_8-0)** Vannier B, Zhu X, Brown D, Birnbaumer L (April 1998). ["The membrane topology of human transient receptor potential 3 as inferred from glycosylation-scanning mutagenesis and epitope immunocytochemistry"](https://doi.org/10.1074%2Fjbc.273.15.8675). *J. Biol. Chem*. **273** (15): 8675–9. [doi](/source/Doi_(identifier)):[10.1074/jbc.273.15.8675](https://doi.org/10.1074%2Fjbc.273.15.8675). [PMID](/source/PMID_(identifier)) [9535843](https://pubmed.ncbi.nlm.nih.gov/9535843).{{[cite journal](https://en.wikipedia.org/wiki/Template:Cite_journal)}}: CS1 maint: multiple names: authors list ([link](https://en.wikipedia.org/wiki/Category:CS1_maint:_multiple_names:_authors_list))

1. **[^](#cite_ref-pmid15728426_9-0)** Montell C (February 2005). "The TRP superfamily of cation channels". *Sci. STKE*. **2005** (272): re3. [doi](/source/Doi_(identifier)):[10.1126/stke.2722005re3](https://doi.org/10.1126%2Fstke.2722005re3). [PMID](/source/PMID_(identifier)) [15728426](https://pubmed.ncbi.nlm.nih.gov/15728426). [S2CID](/source/S2CID_(identifier)) [7326120](https://api.semanticscholar.org/CorpusID:7326120).

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1. **[^](#cite_ref-12)** Mundt N, Spehr M, Lishko PV (July 2018). ["TRPV4 is the temperature-sensitive ion channel of human sperm"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051745). *eLife*. **7**. [doi](/source/Doi_(identifier)):[10.7554/elife.35853](https://doi.org/10.7554%2Felife.35853). [PMC](/source/PMC_(identifier)) [6051745](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051745). [PMID](/source/PMID_(identifier)) [29963982](https://pubmed.ncbi.nlm.nih.gov/29963982).

1. **[^](#cite_ref-13)** Levine JD, Alessandri-Haber N (August 2007). ["TRP channels: targets for the relief of pain"](https://hal.archives-ouvertes.fr/hal-00562760/file/PEER_stage2_10.1016%252Fj.bbadis.2007.01.008.pdf) (PDF). *Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease*. **1772** (8): 989–1003. [doi](/source/Doi_(identifier)):[10.1016/j.bbadis.2007.01.008](https://doi.org/10.1016%2Fj.bbadis.2007.01.008). [PMID](/source/PMID_(identifier)) [17321113](https://pubmed.ncbi.nlm.nih.gov/17321113). [S2CID](/source/S2CID_(identifier)) [11450214](https://api.semanticscholar.org/CorpusID:11450214).

1. ^ [***a***](#cite_ref-pmid17616360_14-0) [***b***](#cite_ref-pmid17616360_14-1) Prevarskaya N, Zhang L, Barritt G (August 2007). ["TRP channels in cancer"](https://hal.archives-ouvertes.fr/hal-00562788/file/PEER_stage2_10.1016%252Fj.bbadis.2007.05.006.pdf) (PDF). *Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease*. **1772** (8): 937–46. [doi](/source/Doi_(identifier)):[10.1016/j.bbadis.2007.05.006](https://doi.org/10.1016%2Fj.bbadis.2007.05.006). [PMID](/source/PMID_(identifier)) [17616360](https://pubmed.ncbi.nlm.nih.gov/17616360).

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1. **[^](#cite_ref-pmid17464295_16-0)** Szallasi A, Cortright DN, Blum CA, Eid SR (May 2007). "The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept". *Nature Reviews. Drug Discovery*. **6** (5): 357–72. [doi](/source/Doi_(identifier)):[10.1038/nrd2280](https://doi.org/10.1038%2Fnrd2280). [PMID](/source/PMID_(identifier)) [17464295](https://pubmed.ncbi.nlm.nih.gov/17464295). [S2CID](/source/S2CID_(identifier)) [6276214](https://api.semanticscholar.org/CorpusID:6276214).

## External links

- [Transient+Receptor+Potential+Channels](https://meshb.nlm.nih.gov/record/ui?name=Transient+Receptor+Potential+Channels) at the U.S. National Library of Medicine [Medical Subject Headings](/source/Medical_Subject_Headings) (MeSH)

- ["Transient Receptor Potential Channels"](https://web.archive.org/web/20211025112234/https://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12). *IUPHAR Database of Receptors and Ion Channels*. International Union of Basic and Clinical Pharmacology. Archived from [the original](http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12) on 2021-10-25. Retrieved 2008-12-17.

- ["TRIP Database"](http://www.trpchannel.org). *a manually curated database of protein-protein interactions for mammalian TRP channels*.

v t e Membrane transport protein: ion channels (TC 1A) Ca2+: Calcium channel Ligand-gated Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3 Voltage-gated L-type/Cavα 1.1 1.2 1.3 1.4 N-type/Cavα2.2 P-type/Cavα 2.1 Q-type/Cavα2.1 R-type/Cavα2.3 T-type/Cavα 3.1 3.2 3.3 α2δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2 Na+: Sodium channel Constitutively active Epithelial sodium channel α β γ δ Proton-gated Amiloride-sensitive cation channel 1 2 3 4 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 K+: Potassium channel Calcium-activated BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 KCa 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1 Inward-rectifier KATP Kir 1.1 2.1 2.2 2.3 2.4 2.6 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 Voltage-gated Kvα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 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 Kvα7-12 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 minK/ISK-like MiRP 1 2 3 Shaker (gene) Miscellaneous Cl−: Chloride channel Calcium-dependent chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B H+: Proton channel HVCN1 M+: CNG cation channel α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4 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 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6 H2O (+ solutes): Porin Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family Cytoplasm: Gap junction Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin By gating mechanism Ion channel class Ligand-gated Light-gated Voltage-gated Stretch-activated see also disorders

v t e TRP channel modulators TRPA Activators 4-Hydroxynonenal 4-Oxo-2-nonenal 5,6-EET 12S-HpETE 15-Deoxy-Δ12,14-prostaglandin J2 α-Sanshool (ginger, Sichuan and melegueta peppers) Acrolein Allicin (garlic) Allyl isothiocyanate (mustard, radish, horseradish, wasabi) AM404 ASP-7663 Bradykinin Cannabichromene (cannabis) Cannabidiol (cannabis) Cannabigerol (cannabis) Cinnamaldehyde (cinnamon) CR gas (dibenzoxazepine; DBO) CS gas (2-chlorobenzal malononitrile) Cuminaldehyde (cumin) Curcumin (turmeric) Dehydroligustilide (celery) Diallyl disulfide Dicentrine (Lindera spp.) Farnesyl thiosalicylic acid Formalin Gingerols (ginger) Hepoxilin A3 Hepoxilin B3 Hydrogen peroxide Icilin Isothiocyanate JT-010 Ligustilide (celery, Angelica acutiloba) Linalool (Sichuan pepper, thyme) Methylglyoxal Methyl salicylate (wintergreen) N-Methylmaleimide Nicotine (tobacco) Oleocanthal (olive oil) Paclitaxel (Pacific yew) PF-4840154 Phenacyl chloride Polygodial (Dorrigo pepper) Shogaols (ginger, Sichuan and melegueta peppers) Tear gases Tetrahydrocannabinol (cannabis) Tetrahydrocannabiorcol Thiopropanal S-oxide (onion) Umbellulone (Umbellularia californica) WIN 55,212-2 Blockers A-967079 AM-0902 Dehydroligustilide (celery) HC-030031 Nicotine (tobacco) PF-04745637 Ruthenium red TRPC Activators Adhyperforin (St John's wort) Diacyl glycerol GSK1702934A Hyperforin (St John's wort) Substance P Blockers DCDPC DHEA-S Flufenamic acid GSK417651A GSK2293017A Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid Niflumic acid Pregnenolone sulfate Progesterone Pyr3 Tolfenamic acid TRPM Activators ADP-ribose BCTC Calcium (intracellular) CIM-0216 Cold Coolact P Cooling Agent 10 Eucalyptol (eucalyptus) Frescolat MGA Frescolat ML Geraniol Hydroxycitronellal Icilin Linalool Menthol (mint) PMD 38 Pregnenolone sulfate Rutamarin (Ruta graveolens) Steviol glycosides (e.g., stevioside) (Stevia rebaudiana) Sweet tastants (e.g., glucose, fructose, sucrose; indirectly) Thio-BCTC WS-12 Blockers AMG-333 Capsazepine Clotrimazole DCDPC Elismetrep Flufenamic acid Meclofenamic acid Mefenamic acid N-(p-Amylcinnamoyl)anthranilic acid Nicotine (tobacco) Niflumic acid Ononetin PF-05105679 RQ-00203078 Ruthenium red Rutamarin (Ruta graveolens) Tolfenamic acid TPPO TRPM4-IN-5 TRPML Activators EVP21 MK6-83 ML-SA1 ML2-SA1 PI(3,5)P2 SF-22 SN-2 Blockers ML-SI3 PI(4,5)P2 TRPP Activators Triptolide (Tripterygium wilfordii) Blockers Ruthenium red TRPV Activators 2-APB 5,6-EET 9-HODE 9-oxoODE 12S-HETE 12S-HpETE 13-HODE 13-oxoODE 20-HETE α-Sanshool (ginger, Sichuan and melegueta peppers) Allicin (garlic) AM404 Anandamide Bisandrographolide (Andrographis paniculata) Camphor (camphor laurel, rosemary, camphorweed, African blue basil, camphor basil) Cannabidiol (cannabis) Cannabidivarin (cannabis) Capsaicin (chili pepper) Carvacrol (oregano, thyme, pepperwort, wild bergamot, others) DHEA Diacyl glycerol Dihydrocapsaicin (chili pepper) Estradiol Eugenol (basil, clove) Evodiamine (Euodia ruticarpa) Gingerols (ginger) GSK1016790A Heat Hepoxilin A3 Hepoxilin B3 Homocapsaicin (chili pepper) Homodihydrocapsaicin (chili pepper) Incensole (incense) Lysophosphatidic acid Low pH (acidic conditions) Menthol (mint) N-Arachidonoyl dopamine N-Oleoyldopamine N-Oleoylethanolamide Nonivamide (PAVA) (PAVA spray) Nordihydrocapsaicin (chili pepper) Paclitaxel (Pacific yew) Paracetamol (acetaminophen) Phenylacetylrinvanil Phorbol esters (e.g., 4α-PDD) Piperine (black pepper, long pepper) Polygodial (Dorrigo pepper) Probenecid Protons RhTx Rutamarin (Ruta graveolens) Resiniferatoxin (RTX) (Euphorbia resinifera/pooissonii) Shogaols (ginger, Sichuan and melegueta peppers) Tetrahydrocannabivarin (cannabis) Thymol (thyme, oregano) Tinyatoxin (Euphorbia resinifera/pooissonii) Tramadol Vanillin (vanilla) Zucapsaicin Blockers α-Spinasterol (Vernonia tweediana) AMG-517 AMG-9810 Asivatrep BCTC Cannabigerol (cannabis) Cannabigerolic acid (cannabis) Cannabigerovarin (cannabis) Cannabinol (cannabis) Capsazepine DCDPC DHEA DHEA-S Flufenamic acid GRC-6211 HC-067047 Lanthanum Mavatrep Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid NGD-8243 Niflumic acid Pregnenolone sulfate RN-1734 RN-9893 Ruthenium red SB-366791 SB-705498 Tivanisiran Tolfenamic acid TRPV3-74a See also: Receptor/signaling modulators • Ion channel modulators

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Adapted from the Wikipedia article [TRPV](https://en.wikipedia.org/wiki/TRPV) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/TRPV?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.