TRPV1

The Transient receptor potential vanilloid 1 or TRPV1 can refer to the TRP cation channel receptor or the gene which encodes it in "Homo sapiens".

TRPV1 is a nonselective ligand-gated cation channel that may be activated by a wide variety of exogenous and endogenous stimuli, including heat greater than 43°C, low pH, anandamide, N-arachidonoyl-dopamine, and capsaicin. TRPV1 receptors are found in the central nervous system and the peripheral nervous system and are involved in the transmission and modulation of pain, as well as the integration of diverse painful stimuli.cite journal | author = Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, Marsh K, Bianchi B, McDonald H, Niforatos W, Neelands TR, Moreland RB, Decker MW, Lee CH, Sullivan JP, Faltynek CR | title = TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists | journal = J. Neurosci. | volume = 26 | issue = 37 | pages = 9385–93 | year = 2006 | pmid = 16971522 | doi = 10.1523/JNEUROSCI.1246-06.2006 | issn = ] cite journal | author = Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V | title = An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 12 | pages = 8400–5 | year = 2002 | pmid = 12060783 | doi = 10.1073/pnas.122196999 | issn = ]

Clinical significance

TRPV1 blockade in vivo elicited hyperthermia in multiple species, from rodents to humans, suggesting that TRPV1 is involved in body temperature maintenance.cite journal | author = Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC | title = The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation | journal = J. Neurosci. | volume = 27 | issue = 13 | pages = 3366–74 | year = 2007 | month = March | pmid = 17392452 | doi = 10.1523/JNEUROSCI.4833-06.2007 | url = | issn = ] Recently, AMG 517, a highly selective TRPV1 antagonist was dropped out of clinical trials due to the undesirable magnitude of hyperthermia.cite journal | author = Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, Akrami A, Alvarez F, Bak A, Darling M, Gore A, Jang GR, Kesslak JP, Ni L, Norman MH, Palluconi G, Rose MJ, Salfi M, Tan E, Romanovsky AA, Banfield C, Davar G | title = Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans | journal = Pain | volume = 136 | issue = 1-2 | pages = 202–10 | year = 2008 | month = May | pmid = 18337008 | doi = 10.1016/j.pain.2008.01.024 | url = | issn = ] A second molecule, SB-705498 was also evaluated in the clinic but its effect on body temperature was not reported.cite journal | author = Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM | title = The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans | journal = Pain | volume = 132 | issue = 1-2 | pages = 132–41 | year = 2007 | month = November | pmid = 17659837 | doi = 10.1016/j.pain.2007.06.006 | url = | issn = ]

Peripheral nervous system

TRPV1 antagonists have shown efficacy in reducing nociception from inflammatory and neuropathic pain models in rats.cite journal | author = Jhaveri MD, Elmes SJ, Kendall DA, Chapman V | title = Inhibition of peripheral vanilloid TRPV1 receptors reduces noxious heat-evoked responses of dorsal horn neurons in naïve, carrageenan-inflamed and neuropathic rats | journal = Eur. J. Neurosci. | volume = 22 | issue = 2 | pages = 361–70 | year = 2005 | pmid = 16045489 | doi = 10.1111/j.1460-9568.2005.04227.x | issn = ] This provides evidence that TRPV1 is the capsaicin's sole receptor.cite journal | author = Story GM, Crus-Orengo L | title = Feel the Burn | journal = American Scientist | volume = 95 | issue = 4 | pages = 326–333 | year = 2008 | pmid = | doi = | issn = 0003-0996 | url = http://www.americanscientist.org/template/AssetDetail/assetid/55542 ]

In humans, drugs acting at TRPV1 receptors could potentially be used to treat neuropathic pain associated with multiple sclerosis, chemotherapy, or amputation, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis.cite journal | author = Gunthorpe MJ, Szallasi A | title = Peripheral TRPV1 receptors as targets for drug development: new molecules and mechanisms | journal = Curr. Pharm. Des. | volume = 14 | issue = 1 | pages = 32–41 | year = 2008 | pmid = 18220816 | doi = | url = http://openurl.ingenta.com/content/nlm?genre=article&issn=1381-6128&volume=14&issue=1&spage=32&aulast=Gunthorpe | issn = ]

The role of TRPV1 in the regulation of body temperature has emerged in last few years. Based on a number of TRPV1 selective antagonists causing an increase in body temperature (hyperthermia), it was proposed that TRPV1 is tonically active in vivo and regulates body temperature.cite journal | author = Gavva NR, Bannon AW, Surapaneni S, Hovland DN Jr, Lehto SG, Gore A, Juan T, Deng H, Han B, Klionsky L, Kuang R, Le A, Tamir R, Wang J, Youngblood B, Zhu D, Norman MH, Magal E, Treanor JJ, Louis JC | title = The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation | journal = J. Neurosci. | volume = 27 | issue = 13 | pages = 3366–74 | year = 2007 | month = March | pmid = 17392452 | doi = 10.1523/JNEUROSCI.4833-06.2007 | url = | issn = ] In a recent report, it was found that tonically active TRPV1 channels are present in the viscera and keep an ongoing suppressive effect on body temperature.cite journal |author=Steiner AA, Turek VF, Almeida MC, Burmeister JJ, Oliveira DL, Roberts JL, Bannon AW, Norman MH, Louis JC, Treanor JJ, Gavva NR, Romanovsky AA | title = Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors | journal = J. Neurosci. | volume = 27 | issue = 28 | pages = 7459–68 | year = 2007 | month = July | pmid = 17626206 | doi = 10.1523/JNEUROSCI.1483-07.2007 | url = ]

Central nervous system

TRPV1 is also expressed at high levels in the central nervous system and has been proposed as a target for treatment of not only pain but also for other conditions such as anxiety.cite journal | author = Starowicz K, Cristino L, Di Marzo V | title = TRPV1 receptors in the central nervous system: potential for previously unforeseen therapeutic applications | journal = Curr. Pharm. Des. | volume = 14 | issue = 1 | pages = 42–54 | year = 2008 | pmid = 18220817 | doi = | url = http://openurl.ingenta.com/content/nlm?genre=article&issn=1381-6128&volume=14&issue=1&spage=42&aulast=Starowicz | issn = ] Furthermore TRPV1 appears to mediate long term depression (LTD) in the hippocampus.cite journal | author = Gibson HE, Edwards JG, Page RS, Van Hook MJ, Kauer JA | title = TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons | journal = Neuron | volume = 57 | issue = 5 | pages = 746–59 | year = 2008 | pmid = 18341994 | doi = 10.1016/j.neuron.2007.12.027 | issn = ] LTD has been linked to a decrease in the ability to make new memories, unlike its opposite long term potentiation (LTP), which aids in memory formation. A dynamic pattern of LTD and LTP occurring at many synapses provides a code for memory formation. Long-term depression and subsequent prunning of dampened down synapses is important in memory formation. In rat brain slices, activation of TRV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD. Hence there may be therapeutic potential in antagonizing TRPV1 in the central nervous system, perhaps as a treatment for epilepsy (TRPV1 is already a target in the peripheral nervous system for pain relief).

ee also

*Capsaicin
*Vanilloid
*Cannabinoid receptor

References

Further reading

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citations =
*cite journal | author = Immke DC, Gavva NR | title = The TRPV1 receptor and nociception | journal = Semin. Cell Dev. Biol. | volume = 17 | issue = 5 | pages = 582–91 | year = 2006 | month = October | pmid = 17196854 | doi = 10.1016/j.semcdb.2006.09.004 | url = | issn =
*cite journal | author=Heiner I, Eisfeld J, Lückhoff A |title=Role and regulation of TRP channels in neutrophil granulocytes. |journal=Cell Calcium |volume=33 |issue= 5-6 |pages= 533–40 |year= 2004 |pmid= 12765698 |doi=
*cite journal | author=Geppetti P, Trevisani M |title=Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function. |journal=Br. J. Pharmacol. |volume=141 |issue= 8 |pages= 1313–20 |year= 2004 |pmid= 15051629 |doi= 10.1038/sj.bjp.0705768
*cite journal | author=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
*cite journal | author=Szallasi A, Cruz F, Geppetti P |title=TRPV1: a therapeutic target for novel analgesic drugs? |journal=Trends in molecular medicine |volume=12 |issue= 11 |pages= 545–54 |year= 2007 |pmid= 16996800 |doi= 10.1016/j.molmed.2006.09.001
*cite journal | author=Pingle SC, Matta JA, Ahern GP |title=Capsaicin receptor: TRPV1 a promiscuous TRP channel. |journal=Handb Exp Pharmacol |volume= |issue= 179 |pages= 155–71 |year= 2007 |pmid= 17217056 |doi= 10.1007/978-3-540-34891-7_9
*cite journal | author=Liddle RA |title=The role of Transient Receptor Potential Vanilloid 1 (TRPV1) channels in pancreatitis. |journal=Biochim. Biophys. Acta |volume=1772 |issue= 8 |pages= 869–78 |year= 2007 |pmid= 17428642 |doi= 10.1016/j.bbadis.2007.02.012

External links

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