TRPM5
| TRPM5 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 11: 2.4 – 2.44 Mb | Chr 7: 142.62 – 142.65 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
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.[5][6]
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
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.[7][8] The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential.[9]
TRPM5 is expressed in pancreatic
tuft cells,[12]
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.[13]
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.[11]
- 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.[14]
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.[15]
- Ketoconazole is an antifungal drug that inhibits TRPM5 activity.[16]
- NSAID drug that inhibits the activity of TRPM5 or TRPM4.[17]
- Clotrimazole is an antifungal drug and reduces the currents through TRPM5.[17]
- Nicotine inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.[18]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000070985 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000009246 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10607831.
- S2CID 17936350.
- PMID 21557960.
- PMID 21653867.
- PMID 20696704.
- PMID 20194741.
- ^ PMID 28361903.
- PMID 17610722.
- )
- PMID 26501253.
- PMID 21158685.
- PMID 29316407.
- ^ PMID 15670874.
- PMID 24452633.
Further reading
- Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, et al. (March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. PMID 28361903.
- Islam MS (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. Vol. 704. Berlin: Springer. p. 700. ISBN 978-94-007-0264-6.
- Liman ER (2007). "TRPM5 and Taste Transduction". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 287–98. PMID 17217064.
- Holzer P (July 2011). "Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system". Pharmacology & Therapeutics. 131 (1): 142–70. PMID 21420431.
- Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P (January 2011). "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology. 162 (1): 18–37. PMID 20804496.
- Liman ER (2010). "Changing Taste by Targeting the Ion Channel TRPM5". The Open Drug Discovery Journal. 2: 98–102. .
- Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D (June 2010). "TRPM5 regulates glucose-stimulated insulin secretion". Pflügers Archiv. 460 (1): 69–76. PMID 20393858.
- Oliveira-Maia AJ, Stapleton-Kotloski JR, Lyall V, Phan TH, Mummalaneni S, Melone P, Desimone JA, Nicolelis MA, Simon SA (February 2009). "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. PMID 19164511.
- Liu D, Zhang Z, Liman ER (May 2005). "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. PMID 15731110.
- Liu D, Liman ER (December 2003). "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. PMID 14657398.
- Wu LJ, Sweet TB, Clapham DE (September 2010). "International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family". Pharmacological Reviews. 62 (3): 381–404. PMID 20716668.
External links
- TRPM5+protein,+human at the U.S. 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.