Biology:TRPM5

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the TRPM5 gene.

Function

TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells. Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K⁺ and Na⁺. TRPM5 is a key component of taste transduction in the gustatory system of bitter, sweet and umami tastes being activated by high levels of intracellular calcium. It has also been targeted as a possible contributor to fat taste signaling. The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential.

TRPM5 is expressed in pancreatic β-cells where it is involved in the signaling mechanism for insulin secretion. The potentiation of TRPM5 in the β-cells leads to increased insulin secretion and protects against the development of type 2 diabetes in mice. Further expression of TRPM5 can be found in tuft cells, solitary chemosensory cells and several other cell types in the body that have a sensory role.

Drugs modulating TRPM5

The role of TRPM5 in the pancreatic β-cell makes it a target for the development of novel antidiabetic therapies.

Agonists

• Steviol glycosides, the sweet compounds in the leaves of the Stevia rebaudiana plant, potentiate the calcium-induced activity of TRPM5. In this way they stimulate the glucose-induced insulin secretion from the pancreatic β-cell.
• Rutamarin, a phytochemical found in Ruta graveolens has been identified as an activator of several TRP channels, including TRPM5 and TRPV1 and inhibits the activity of TRPM8.

Antagonists

Selective blocking agents of TRPM5 ion channels can be used to identify TRPM5 currents in primary cells. Most identified compounds show, however, a poor selectivity between TRPM4 and TRPM5 or other ion channels.

• TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility.
• Ketoconazole is an antifungal drug that inhibits TRPM5 activity.
• Flufenamic Acid is an NSAID drug that inhibits the activity of TRPM5 or TRPM4.
• Clotrimazole is an antifungal drug and reduces the currents through TRPM5.
• Nicotine inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.

See also

• TRPM

Further reading

• "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications 8: 14733. March 2017. doi:10.1038/ncomms14733. PMID 28361903. Bibcode: 2017NatCo...814733P. 
• Islam, Md. Shahidul (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. 704. Berlin: Springer. pp. 700. ISBN 978-94-007-0264-6. 
• "TRPM5 and Taste Transduction". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. 179. 2007. pp. 287–98. doi:10.1007/978-3-540-34891-7_17. ISBN 978-3-540-34889-4. 
• "Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system". Pharmacology & Therapeutics 131 (1): 142–70. July 2011. doi:10.1016/j.pharmthera.2011.03.006. PMID 21420431. 
• "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology 162 (1): 18–37. January 2011. doi:10.1111/j.1476-5381.2010.01009.x. PMID 20804496. 
• "Changing Taste by Targeting the Ion Channel TRPM5". The Open Drug Discovery Journal 2: 98–102. 2010. doi:10.2174/1875039701407010001. 
• "TRPM5 regulates glucose-stimulated insulin secretion". Pflügers Archiv 460 (1): 69–76. June 2010. doi:10.1007/s00424-010-0835-z. PMID 20393858. 
• "Nicotine activates TRPM5-dependent and independent taste pathways". Proceedings of the National Academy of Sciences of the United States of America 106 (5): 1596–601. February 2009. doi:10.1073/pnas.0810184106. PMID 19164511. Bibcode: 2009PNAS..106.1596O. 
• "Extracellular acid block and acid-enhanced inactivation of the Ca2+-activated cation channel TRPM5 involve residues in the S3-S4 and S5-S6 extracellular domains". The Journal of Biological Chemistry 280 (21): 20691–9. May 2005. doi:10.1074/jbc.M414072200. PMID 15731110. 
• "Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5". Proceedings of the National Academy of Sciences of the United States of America 100 (25): 15160–5. December 2003. doi:10.1073/pnas.2334159100. PMID 14657398. Bibcode: 2003PNAS..10015160L. 
• "International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family". Pharmacological Reviews 62 (3): 381–404. September 2010. doi:10.1124/pr.110.002725. PMID 20716668. 

External links

• TRPM5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• IUPHAR
• HGNC Gene families
• Pfam

This article incorporates text from the United States National Library of Medicine, which is in the public domain.