TRPM8: Difference between revisions
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Revision as of 11:38, 17 December 2008
Template:PBB Transient receptor potential cation channel, subfamily M, member 8, also known as TRPM8, is a protein which in humans is encoded by the TRPM8 gene.[1]
Function
TRPM8 is an ion channel, upon activation it allows the entry of Na+ (sodium) and Ca2+ (calcium) ions to the cell that leads to depolarization and the generation of action potential. This eventually leads to the feeling of cold.
The TRPM8 protein is expresed in sensory neurons, and it is activated by cold temperatures and cooling agents, such as menthol and icilin where as WS-12 and CPS-369 are the most selective agonist of TRPM8.[2][3]
Clinical significance
Cold-patches have traditionally been used to induce analgesia or relief in pain which is caused as result of traumatic injuries. The underlying mechanism of cold-induced analgesia remained obscure till the discovery of TRPM8.
Three independent research groups have reported that mice lacking TRPM8 gene are severely impaired in their ability to detect cold temperatures.[4] Remarkably, these animals are deficient in many diverse aspects of cold signaling, including cool and noxious cold perception, injury-evoked sensitization to cold, and cooling-induced analgesia. These animals provide a great deal of insight into the molecular signaling pathways that participate in the detection of cold and painful stimuli. Many research groups, both in universities and pharmaceutical companies, are now actively involved in looking for selective TRPM8 ligands to be used as new generation of neuropathic analgesic drugs. Interestingly, low concentrations of TRPM8 agonists such as menthol (or icilin) found to be antihyperalgesic in certain conditions,[5] whereas high concentrations of menthol caused both cold and mechanical hyperalgesia in healthy volunteers.[6]
TRPM8 knockout mice not only indicated that TRPM8 is required for cold sensation but also revealed that TRPM8 mediates both cold and mechanical allodynia in rodent models of neuropathic pain.[7] Furthermore, recently it was shown that TRPM8 antagonists are effective in reversing established pain in neuropathic and visceral pain models.[8]
TRPM8 upregulation in bladder tissues correlates with pain in patients with painful bladder syndromes.[9] Furthermore, TRPM8 is upregulated in many prostate cancer cell lines and Dendreon/Genentech are pursuing an agonist approach to induce apoptosis and prostate cancer cell death.[10]
See also
References
- ^ Clapham DE, Julius D, Montell C, Schultz G (2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological reviews. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Sherkheli; et al. (2007). "Selective TRPM8 agonists: a novel group of neurophathic analgesics". FEBS Journal. 274 (s1): 232. doi:10.1111/j.0014-2956.2007.05861_4.x.
{{cite journal}}: Cite has empty unknown parameter:|month=(help); Explicit use of et al. in:|author=(help) - ^ Ma S, G G, Ak VE, Jf D, H H (2008). "Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels". Pak J Pharm Sci. 21 (4): 370–8. PMID 18930858.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Daniels RL, McKemy DD (2007). "Mice left out in the cold: commentary on the phenotype of TRPM8-nulls". Mol Pain. 3: 23. doi:10.1186/1744-8069-3-23. PMC 1988789. PMID 17705869.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, Robertson DC, Fleetwood-Walker SM, Mitchell R (2006). "Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain". Current biology : CB. 16 (16): 1591–605. doi:10.1016/j.cub.2006.07.061. PMID 16920620.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Wasner G, Schattschneider J, Binder A, Baron R (2004). "Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors". Brain : a journal of neurology. 127 (Pt 5): 1159–71. doi:10.1093/brain/awh134. PMID 14985268.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Colburn RW, Lubin ML, Stone DJ Jr, Wang Y, Lawrence D, D'Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N (2007). "Attenuated cold sensitivity in TRPM8 null mice". Neuron. 54 (3): 379–86. doi:10.1016/j.neuron.2007.04.017. PMID 17481392.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X (2008). American journal of physiology. Renal physiology. 295 (3): F803–10. doi:10.1152/ajprenal.90269.2008. PMID 18562636.
{{cite journal}}: Missing or empty|title=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P (2006). "Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations". BMC urology. 6: 6. doi:10.1186/1471-2490-6-6. PMC 1420318. PMID 16519806.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ "Dendreon: Targeting Cancer, Transforming Lives". Dendreon Corporation. 2005-09-21. Retrieved 2008-10-31.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help)
Further reading
External links
- "Transient Receptor Potential Channels: TRPM8". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - TRPM8+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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