TRPV

Functional TRPV ion channels are tetrameric 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.{{cite journal | vauthors = Vennekens R, Owsianik G, Nilius B | title = Vanilloid transient receptor potential cation channels: an overview | journal = Current Pharmaceutical Design | volume = 14 | issue = 1 | pages = 18–31 | year = 2008 | pmid = 18220815 | doi = 10.2174/138161208783330763 | url = https://lirias.kuleuven.be/handle/123456789/200319 | url-access = subscription }}{{cite journal |author=Cheng W, Yang F, Takanishi CL, Zheng J |title=Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties |journal=J. Gen. Physiol. |volume=129 |issue=3 |pages=191–207 |date=March 2007 |pmid=17325193 |pmc=2151614 |doi=10.1085/jgp.200709731 }}

The TRPV channel monomeric subunit components each contain six transmembrane (TM) domains (designated S1–S6) with a pore domain between the fifth (S5) and sixth (S6) segments.{{cite journal | author = Vannier B, Zhu X, Brown D, Birnbaumer L | title = The membrane topology of human transient receptor potential 3 as inferred from glycosylation-scanning mutagenesis and epitope immunocytochemistry | journal = J. Biol. Chem. | volume = 273 | issue = 15 | pages = 8675–9 |date=April 1998 | pmid = 9535843 | doi = 10.1074/jbc.273.15.8675| doi-access = free}} TRPV subunits contain three to five N-terminal ankyrin repeats.{{cite journal | author = Montell C | title = The TRP superfamily of cation channels | journal = Sci. STKE | volume = 2005 | issue = 272 | pages = re3 |date=February 2005 | pmid = 15728426 | doi = 10.1126/stke.2722005re3 | s2cid = 7326120 }}

TRPV proteins respond to the taste of garlic (allicin). TRPV1 contributes to heat and inflammation sensations and mediates the pungent odor and pain sensations associated with capsaicin and piperine.

The table below summarizes the functions and properties of the individual TRPV channel family members:{{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 = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 427–50 | date = December 2005 | pmid = 16382100 | doi = 10.1124/pr.57.4.6 | s2cid = 17936350 }}{{cite journal | vauthors = Venkatachalam K, Montell C | title = TRP channels | journal = Annual Review of Biochemistry | volume = 76 | issue = 1 | pages = 387–417 | year = 2007 | pmid = 17579562 | doi = 10.1146/annurev.biochem.75.103004.142819 | pmc = 4196875 }}

Mutations in TRPs have been linked to neurodegenerative disorders, skeletal dysplasia, kidney disorders, 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.{{cite journal | vauthors = Levine JD, Alessandri-Haber N | title = TRP channels: targets for the relief of pain | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 8 | pages = 989–1003 | date = August 2007 | pmid = 17321113 | doi = 10.1016/j.bbadis.2007.01.008 | s2cid = 11450214 | url = https://hal.archives-ouvertes.fr/hal-00562760/file/PEER_stage2_10.1016%252Fj.bbadis.2007.01.008.pdf }} For instance, the use of TRPV1 agonists would potentially inhibit nociception at TRPV1, particularly in pancreatic tissue where TRPV1 is highly expressed.{{cite journal | vauthors = Prevarskaya N, Zhang L, Barritt G | title = TRP channels in cancer | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 8 | pages = 937–46 | date = August 2007 | pmid = 17616360 | doi = 10.1016/j.bbadis.2007.05.006 | url = https://hal.archives-ouvertes.fr/hal-00562788/file/PEER_stage2_10.1016%252Fj.bbadis.2007.05.006.pdf }} The TRPV1 agonist capsaicin, found in chili peppers, has been indicated to relieve neuropathic pain. TRPV1 antagonists inhibit nociception at TRPV1.

Altered expression of TRP proteins often leads to tumorigenesis, clearly seen in TRPM1. 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 and necrosis. Much research remains to be done as to whether TRP channel mutations lead to cancer progression or whether they are associated mutations.

Four TRPVs (TRPV1, TRPV2, TRPV3, and TRPV4) are expressed in afferent nociceptors, 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.{{cite journal | author = Levine JD, Alessandri-Haber N | title = TRP channels: targets for the relief of pain | journal = Biochim. Biophys. Acta | volume = 1772 | issue = 8 | pages = 989–1003 |date=August 2007 | pmid = 17321113 | doi = 10.1016/j.bbadis.2007.01.008 | s2cid = 11450214 | url = https://hal.archives-ouvertes.fr/hal-00562760/file/PEER_stage2_10.1016%252Fj.bbadis.2007.01.008.pdf}} A number of TRPV1 selective blockers such as resiniferatoxin are currently in clinical trials for the treatment of various types of pain.{{cite journal | vauthors = Szallasi A, Cortright DN, Blum CA, Eid SR | title = The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept | journal = Nature Reviews. Drug Discovery | volume = 6 | issue = 5 | pages = 357–72 | date = May 2007 | pmid = 17464295 | doi = 10.1038/nrd2280 | s2cid = 6276214 }}

• Discovery and development of TRPV1 antagonists
• TRPA1

{{Reflist|32em}}

• {{MeshName|Transient+Receptor+Potential+Channels}}
• {{cite web | url = http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12 | title = Transient Receptor Potential Channels | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2008-12-17 | archive-date = 2021-10-25 | archive-url = https://web.archive.org/web/20211025112234/https://www.iuphar-db.org/IC/FamilyMenuForward?familyId=12 | url-status = dead }}
• {{cite web | url = http://www.trpchannel.org | title = TRIP Database | work = a manually curated database of protein-protein interactions for mammalian TRP channels}}

{{Ion channels|g4}}

{{Transient receptor potential channel modulators}}

Category:Membrane proteins

Category:Ion channels