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 TRPM5gene.[1][2]
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.[3][4] The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential.[5]
TRPM5 is expressed in pancreatic β-cells[6] 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.[7] Further expression of TRPM5 can be found in tuft cells,[8] 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.[9]
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.[7]
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.[10]
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.[11]
Ketoconazole is an antifungal drug that inhibits TRPM5 activity.[12]
↑Prawitt D, Enklaar T, Klemm G, Gärtner B, Spangenberg C, Winterpacht A, Higgins M, Pelletier J, Zabel B (January 2000). "Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression". Human Molecular Genetics. 9 (2): 203–16. doi:10.1093/hmg/9.2.203. PMID10607831.
↑Clapham DE, Julius D, Montell C, Schultz G (December 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. PMID16382100.
↑Mancuso G, Borgonovo G, Scaglioni L, Bassoli A (October 2015). "Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception". Molecules. 20 (10): 18907–22. doi:10.3390/molecules201018907. PMID26501253.
↑Palmer RK, Atwal K, Bakaj I, Carlucci-Derbyshire S, Buber MT, Cerne R, Cortés RY, Devantier HR, Jorgensen V, Pawlyk A, Lee SP, Sprous DG, Zhang Z, Bryant R (December 2010). "Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel". Assay and Drug Development Technologies. 8 (6): 703–13. doi:10.1089/adt.2010.0334. PMID21158685.
↑ 13.013.1Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B (March 2005). "Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice". Cell Calcium. 37 (3): 267–78. doi:10.1016/j.ceca.2004.11.001. PMID15670874.
↑Gees M, Alpizar YA, Luyten T, Parys JB, Nilius B, Bultynck G, Voets T, Talavera K (May 2014). "Differential effects of bitter compounds on the taste transduction channels TRPM5 and IP3 receptor type 3". Chemical Senses. 39 (4): 295–311. doi:10.1093/chemse/bjt115. PMID24452633.
Islam MS (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. 704. Berlin: Springer. p. 700. ISBN978-94-007-0264-6.
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. doi:10.1074/jbc.M414072200. PMID15731110.