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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<sup>+</sup> and Na<sup>+</sup>.
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<sup>+</sup> and Na<sup>+</sup>.
TRPM5 is a key component of [[taste]] transduction in the [[gustatory system]] of [[Bitter (taste)|bitter]], [[sweet]] and [[umami]] tastes being activated by high levels of intracellular [[calcium in biology|calcium]]. It has also been targeted as a possible contributor to fat [[taste]] signaling.<ref>{{pmid|21557960}}</ref><ref>{{pmid|21653867}}</ref> The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an [[action potential]].<ref name="pmid20696704">{{cite journal | vauthors = Chaudhari N, Roper SD | title = The cell biology of taste | journal = J. Cell Biol. | volume = 190 | issue = 3 | pages = 285–96 |date=August 2010 | pmid = 20696704 | pmc = 2922655 | doi = 10.1083/jcb.201003144 }}</ref>
TRPM5 is a key component of [[taste]] transduction in the [[gustatory system]] of [[Bitter (taste)|bitter]], [[sweet]] and [[umami]] tastes being activated by high levels of intracellular [[calcium in biology|calcium]]. It has also been targeted as a possible contributor to fat [[taste]] signaling.<ref>{{cite journal | vauthors = Mattes RD | title = Accumulating evidence supports a taste component for free fatty acids in humans | journal = Physiology & Behavior | volume = 104 | issue = 4 | pages = 624–31 | date = September 2011 | pmid = 21557960 | doi = 10.1016/j.physbeh.2011.05.002 | pmc = 3139746 }}</ref><ref>{{cite journal | vauthors = Liu P, Shah BP, Croasdell S, Gilbertson TA | title = Transient receptor potential channel type M5 is essential for fat taste | journal = The Journal of Neuroscience | volume = 31 | issue = 23 | pages = 8634–42 | date = June 2011 | pmid = 21653867 | doi = 10.1523/JNEUROSCI.6273-10.2011 | pmc = 3125678 }}</ref> The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an [[action potential]].<ref name="pmid20696704">{{cite journal | vauthors = Chaudhari N, Roper SD | title = The cell biology of taste | journal = The Journal of Cell Biology | volume = 190 | issue = 3 | pages = 285–96 | date = August 2010 | pmid = 20696704 | pmc = 2922655 | doi = 10.1083/jcb.201003144 }}</ref>


TRPM5 is expressed in pancreatic [[beta cell|β-cells]]<ref>{{cite journal|last1=Colsoul|first1=B.|last2=Schraenen|first2=A.|last3=Lemaire|first3=K.|last4=Quintens|first4=R.|last5=Van Lommel|first5=L.|last6=Segal|first6=A.|last7=Owsianik|first7=G.|last8=Talavera|first8=K.|last9=Voets|first9=T.|last10=Margolskee|first10=R. F.|last11=Kokrashvili|first11=Z.|last12=Gilon|first12=P.|last13=Nilius|first13=B.|last14=Schuit|first14=F. C.|last15=Vennekens|first15=R.|title=Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice|journal=Proceedings of the National Academy of Sciences|date=1 March 2010|volume=107|issue=11|pages=5208–5213|doi=10.1073/pnas.0913107107|url=http://www.pnas.org/content/107/11/5208}}</ref> 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.<ref name=Philippaert2017>{{cite journal|last1=Philippaert|first1=Koenraad|last2=Pironet|first2=Andy|last3=Mesuere|first3=Margot|last4=Sones|first4=William|last5=Vermeiren|first5=Laura|last6=Kerselaers|first6=Sara|last7=Pinto|first7=Sílvia|last8=Segal|first8=Andrei|last9=Antoine|first9=Nancy|last10=Gysemans|first10=Conny|last11=Laureys|first11=Jos|last12=Lemaire|first12=Katleen|last13=Gilon|first13=Patrick|last14=Cuypers|first14=Eva|last15=Tytgat|first15=Jan|last16=Mathieu|first16=Chantal|last17=Schuit|first17=Frans|last18=Rorsman|first18=Patrik|last19=Talavera|first19=Karel|last20=Voets|first20=Thomas|last21=Vennekens|first21=Rudi|title=Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity|journal=Nature Communications|date=31 March 2017|volume=8|pages=14733|doi=10.1038/ncomms14733|url=http://www.nature.com/articles/ncomms14733}}</ref> Further expression of TRPM5 can be found in [[tuft cells]],<ref>{{cite journal|last1=Kaske|first1=S|last2=Krasteva|first2=G|last3=König|first3=P|last4=Kummer|first4=W|last5=Hofmann|first5=T|last6=Gudermann|first6=T|last7=Chubanov|first7=V|title=TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells.|journal=BMC Neuroscience|date=4 July 2007|volume=8|pages=49|pmid=17610722}}</ref> solitary chemosensory cells and several other cell types in the body that have a sensory role.
TRPM5 is expressed in pancreatic [[beta cell|β-cells]]<ref>{{cite journal | vauthors = Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF, Kokrashvili Z, Gilon P, Nilius B, Schuit FC, Vennekens R | title = Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 11 | pages = 5208–13 | date = March 2010 | pmid = 20194741 | doi = 10.1073/pnas.0913107107 | url = http://www.pnas.org/content/107/11/5208 | pmc = 2841940 }}</ref> 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.<ref name=Philippaert2017>{{cite journal | vauthors = Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, Pinto S, Segal A, Antoine N, Gysemans C, Laureys J, Lemaire K, Gilon P, Cuypers E, Tytgat J, Mathieu C, Schuit F, Rorsman P, Talavera K, Voets T, Vennekens R | title = Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity | journal = Nature Communications | volume = 8 | pages = 14733 | date = March 2017 | pmid = 28361903 | pmc = 5380970 | doi = 10.1038/ncomms14733 | url = http://www.nature.com/articles/ncomms14733 }}</ref> Further expression of TRPM5 can be found in [[tuft cells]],<ref>{{cite journal | vauthors = Kaske S, Krasteva G, König P, Kummer W, Hofmann T, Gudermann T, Chubanov V | title = TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells | journal = BMC Neuroscience | volume = 8 | pages = 49 | date = July 2007 | pmid = 17610722 | pmc = 1931605 | doi = 10.1186/1471-2202-8-49 }}</ref> solitary chemosensory cells and several other cell types in the body that have a sensory role.


== Drugs modulating TRPM5 ==
== Drugs modulating TRPM5 ==
The role of TRPM5 in the pancreatic β-cell makes it a target for the development of novel antidiabetic therapies.<ref>{{cite journal|last1=Philippaert|first1=Koenraad|last2=Vennekens|first2=Rudi|title=Chapter 19 - Transient Receptor Potential (TRP) Cation Channels in Diabetes|journal=TRP Channels as Therapeutic Targets|date=1 January 2015|pages=343–363|url=http://www.sciencedirect.com/science/article/pii/B9780124200241000199|publisher=Academic Press}}</ref>
The role of TRPM5 in the pancreatic β-cell makes it a target for the development of novel antidiabetic therapies.<ref>{{cite journal|last1=Philippaert|first1=Koenraad|last2=Vennekens|first2=Rudi|title=Chapter 19 - Transient Receptor Potential (TRP) Cation Channels in Diabetes|journal=TRP Channels as Therapeutic Targets|date=1 January 2015|pages=343–363|url=http://www.sciencedirect.com/science/article/pii/B9780124200241000199|publisher=Academic Press|doi=10.1016/B978-0-12-420024-1.00019-9}}</ref>


=== Agonists ===
=== Agonists ===
* [[Steviol glycoside]]s, 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.<ref name=Philippaert2017 />
* [[Steviol glycoside]]s, 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.<ref name=Philippaert2017 />
* 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]].<ref>{{cite journal|last1=Mancuso|first1=G|last2=Borgonovo|first2=G|last3=Scaglioni|first3=L|last4=Bassoli|first4=A|title=Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.|journal=Molecules (Basel, Switzerland)|date=16 October 2015|volume=20|issue=10|pages=18907–22|pmid=26501253}}</ref>
* 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]].<ref>{{cite journal | vauthors = Mancuso G, Borgonovo G, Scaglioni L, Bassoli A | title = Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception | journal = Molecules | volume = 20 | issue = 10 | pages = 18907–22 | date = October 2015 | pmid = 26501253 | doi = 10.3390/molecules201018907 }}</ref>


=== Antagonists ===
=== 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.  
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.<ref>{{cite journal|last1=Palmer|first1=RK|last2=Atwal|first2=K|last3=Bakaj|first3=I|last4=Carlucci-Derbyshire|first4=S|last5=Buber|first5=MT|last6=Cerne|first6=R|last7=Cortés|first7=RY|last8=Devantier|first8=HR|last9=Jorgensen|first9=V|last10=Pawlyk|first10=A|last11=Lee|first11=SP|last12=Sprous|first12=DG|last13=Zhang|first13=Z|last14=Bryant|first14=R|title=Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel.|journal=Assay and drug development technologies|date=December 2010|volume=8|issue=6|pages=703–13|pmid=21158685}}</ref>  
* TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility.<ref>{{cite journal | vauthors = 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 | title = Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel | journal = Assay and Drug Development Technologies | volume = 8 | issue = 6 | pages = 703–13 | date = December 2010 | pmid = 21158685 | doi = 10.1089/adt.2010.0334 }}</ref>
* [[Flufenamic acid|Flufenamic Acid]] is a [[NSAID]] drug that inhibits the activity of TRPM5 or TRPM4.<ref name="Ullrich2005">{{cite journal|last1=Ullrich|first1=ND|last2=Voets|first2=T|last3=Prenen|first3=J|last4=Vennekens|first4=R|last5=Talavera|first5=K|last6=Droogmans|first6=G|last7=Nilius|first7=B|title=Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice.|journal=Cell calcium|date=March 2005|volume=37|issue=3|pages=267–78|pmid=15670874}}</ref>
* [[Ketoconazole]] is an antifungal drug that inhibits TRPM5 activity.<ref>{{cite journal | vauthors = Philippaert K, Kerselaers S, Voets T, Vennekens R | title = 2+-Activated Monovalent Cation-Selective Channels | journal = SLAS Discovery | pages = 2472555217748932 | date = January 2018 | pmid = 29316407 | doi = 10.1177/2472555217748932 | url = http://journals.sagepub.com/doi/10.1177/2472555217748932 }}</ref>
* [[Flufenamic acid|Flufenamic Acid]] is a [[NSAID]] drug that inhibits the activity of TRPM5 or TRPM4.<ref name="Ullrich2005">{{cite journal | vauthors = Ullrich ND, Voets T, Prenen J, Vennekens R, Talavera K, Droogmans G, Nilius B | title = Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice | journal = Cell Calcium | volume = 37 | issue = 3 | pages = 267–78 | date = March 2005 | pmid = 15670874 | doi = 10.1016/j.ceca.2004.11.001 }}</ref>
* [[Clotrimazole]] is an antifungal drug and reduces the currents through TRPM5.<ref name="Ullrich2005" />
* [[Clotrimazole]] is an antifungal drug and reduces the currents through TRPM5.<ref name="Ullrich2005" />
* [[Nicotine]] inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.<ref>{{cite journal|last1=Gees|first1=M|last2=Alpizar|first2=YA|last3=Luyten|first3=T|last4=Parys|first4=JB|last5=Nilius|first5=B|last6=Bultynck|first6=G|last7=Voets|first7=T|last8=Talavera|first8=K|title=Differential effects of bitter compounds on the taste transduction channels TRPM5 and IP3 receptor type 3.|journal=Chemical senses|date=May 2014|volume=39|issue=4|pages=295–311|pmid=24452633}}</ref>
* [[Nicotine]] inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.<ref>{{cite journal | vauthors = Gees M, Alpizar YA, Luyten T, Parys JB, Nilius B, Bultynck G, Voets T, Talavera K | title = Differential effects of bitter compounds on the taste transduction channels TRPM5 and IP3 receptor type 3 | journal = Chemical Senses | volume = 39 | issue = 4 | pages = 295–311 | date = May 2014 | pmid = 24452633 | doi = 10.1093/chemse/bjt115 }}</ref>


== See also ==
== See also ==
* [[TRPM]]
* [[TRPM]]
== References ==
{{Reflist|32em}}


== Further reading ==
== Further reading ==
{{refbegin | 2}}
{{refbegin|32em}}
* {{cite journal|last1=Philippaert|first1=K|last2=Pironet|first2=A|last3=Mesuere|first3=M|last4=Sones|first4=W|last5=Vermeiren|first5=L|last6=Kerselaers|first6=S|last7=Pinto|first7=S|last8=Segal|first8=A|last9=Antoine|first9=N|last10=Gysemans|first10=C|last11=Laureys|first11=J|last12=Lemaire|first12=K|last13=Gilon|first13=P|last14=Cuypers|first14=E|last15=Tytgat|first15=J|last16=Mathieu|first16=C|last17=Schuit|first17=F|last18=Rorsman|first18=P|last19=Talavera|first19=K|last20=Voets|first20=T|last21=Vennekens|first21=R|title=Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity.|journal=Nature Communications|date=31 March 2017|volume=8|pages=14733|pmid=28361903}}
* {{cite journal | vauthors = Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, Pinto S, Segal A, Antoine N, Gysemans C, Laureys J, Lemaire K, Gilon P, Cuypers E, Tytgat J, Mathieu C, Schuit F, Rorsman P, Talavera K, Voets T, Vennekens R | display-authors = 6 | title = Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity | journal = Nature Communications | volume = 8 | pages = 14733 | date = March 2017 | pmid = 28361903 | pmc = 5380970 | doi = 10.1038/ncomms14733 }}
* {{cite book | last = Islam | first = Md. Shahidul | title = Transient Receptor Potential Channels |date=January 2011 | volume = 704 | publisher = Springer |  location = Berlin | pages = 700  | series = Advances in Experimental Medicine and Biology | isbn = 978-94-007-0264-6 }}
* {{cite book | last = Islam | first = Md. Shahidul | name-list-format = vanc | title = Transient Receptor Potential Channels |date=January 2011 | volume = 704 | publisher = Springer |  location = Berlin | pages = 700  | series = Advances in Experimental Medicine and Biology | isbn = 978-94-007-0264-6 }}
* {{cite journal | vauthors = Liman ER | title = TRPM5 and taste transduction | journal = Handbook of Experimental Pharmacology | volume = 179 | issue = 179 | pages = 287–98 | year = 2007 | pmid = 17217064 | doi = 10.1007/978-3-540-34891-7_17 | isbn = 978-3-540-34889-4 | series = Handbook of Experimental Pharmacology }}
* {{cite journal | vauthors = Liman ER | title = TRPM5 and taste transduction | journal = Handbook of Experimental Pharmacology | volume = 179 | issue = 179 | pages = 287–98 | year = 2007 | pmid = 17217064 | doi = 10.1007/978-3-540-34891-7_17 | isbn = 978-3-540-34889-4 | series = Handbook of Experimental Pharmacology }}
* {{cite journal | vauthors = Holzer P | title = Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system | journal = Pharmacology & Therapeutics | volume = 131 | issue = 1 | pages = 142–70 | date = July 2011 | pmid = 21420431 | pmc = 3107431 | doi = 10.1016/j.pharmthera.2011.03.006 }}
* {{cite journal | vauthors = Holzer P | title = Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system | journal = Pharmacology & Therapeutics | volume = 131 | issue = 1 | pages = 142–70 | date = July 2011 | pmid = 21420431 | pmc = 3107431 | doi = 10.1016/j.pharmthera.2011.03.006 }}
* {{cite journal | vauthors = Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P | title = TRP channels in neurogastroenterology: opportunities for therapeutic intervention | journal = British Journal of Pharmacology | volume = 162 | issue = 1 | pages = 18–37 | date = January 2011 | pmid = 20804496 | pmc = 3012403 | doi = 10.1111/j.1476-5381.2010.01009.x }}
* {{cite journal | vauthors = Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P | title = TRP channels in neurogastroenterology: opportunities for therapeutic intervention | journal = British Journal of Pharmacology | volume = 162 | issue = 1 | pages = 18–37 | date = January 2011 | pmid = 20804496 | pmc = 3012403 | doi = 10.1111/j.1476-5381.2010.01009.x }}
* {{cite journal | vauthors = Liman ER | title = Changing Taste by Targeting the Ion Channel TRPM5 | journal = The Open Drug Discovery Journal | volume = 2 | issue =  | pages = 98–102 | year = 2010 | pmid =  | doi =  10.2174/1875039701407010001 }}
* {{cite journal | vauthors = Liman ER | title = Changing Taste by Targeting the Ion Channel TRPM5 | journal = The Open Drug Discovery Journal | volume = 2 | issue =  | pages = 98–102 | year = 2010 | pmid =  | doi =  10.2174/1875039701407010001 }}
* {{cite journal | vauthors = Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D | title = TRPM5 regulates glucose-stimulated insulin secretion | journal = Pflugers Archiv | volume = 460 | issue = 1 | pages = 69–76 | date = June 2010 | pmid = 20393858 | doi = 10.1007/s00424-010-0835-z }}
* {{cite journal | vauthors = Brixel LR, Monteilh-Zoller MK, Ingenbrandt CS, Fleig A, Penner R, Enklaar T, Zabel BU, Prawitt D | title = TRPM5 regulates glucose-stimulated insulin secretion | journal = Pflügers Archiv | volume = 460 | issue = 1 | pages = 69–76 | date = June 2010 | pmid = 20393858 | doi = 10.1007/s00424-010-0835-z }}
* {{cite journal | vauthors = Oliveira-Maia AJ, Stapleton-Kotloski JR, Lyall V, Phan TH, Mummalaneni S, Melone P, Desimone JA, Nicolelis MA, Simon SA | title = Nicotine activates TRPM5-dependent and independent taste pathways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 5 | pages = 1596–601 | date = February 2009 | pmid = 19164511 | pmc = 2635785 | doi = 10.1073/pnas.0810184106 }}
* {{cite journal | vauthors = Oliveira-Maia AJ, Stapleton-Kotloski JR, Lyall V, Phan TH, Mummalaneni S, Melone P, Desimone JA, Nicolelis MA, Simon SA | title = Nicotine activates TRPM5-dependent and independent taste pathways | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 5 | pages = 1596–601 | date = February 2009 | pmid = 19164511 | pmc = 2635785 | doi = 10.1073/pnas.0810184106 }}
* {{cite journal | vauthors = Liu D, Zhang Z, Liman ER | title = 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 | journal = The Journal of Biological Chemistry | volume = 280 | issue = 21 | pages = 20691–9 | date = May 2005 | pmid = 15731110 | doi = 10.1074/jbc.M414072200 | last-author-amp = yes }}
* {{cite journal | vauthors = Liu D, Zhang Z, Liman ER | title = 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 | journal = The Journal of Biological Chemistry | volume = 280 | issue = 21 | pages = 20691–9 | date = May 2005 | pmid = 15731110 | doi = 10.1074/jbc.M414072200 | last-author-amp = yes }}
Line 44: Line 48:
* {{MeshName|TRPM5+protein,+human}}
* {{MeshName|TRPM5+protein,+human}}
* [http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?familyId=78&objectId=497 IUPHAR]
* [http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?familyId=78&objectId=497 IUPHAR]
* [http://www.genenames.org/data/hgnc_data.php?hgnc_id=14323 HGNC Gene families]
* [https://www.genenames.org/data/hgnc_data.php?hgnc_id=14323 HGNC Gene families]
* [http://pfam.sanger.ac.uk/protein/Q9NZQ8 Pfam]
* [http://pfam.sanger.ac.uk/protein/Q9NZQ8 Pfam]
== References ==
{{Reflist}}


{{NLM content}}
{{NLM content}}

Latest revision as of 12:45, 5 June 2018

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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.[1][2]

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.[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]
  • Flufenamic Acid is a NSAID drug that inhibits the activity of TRPM5 or TRPM4.[13]
  • Clotrimazole is an antifungal drug and reduces the currents through TRPM5.[13]
  • Nicotine inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.[14]

See also

References

  1. ↑ 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. PMID 10607831.
  2. ↑ 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. PMID 16382100.
  3. ↑ Mattes RD (September 2011). "Accumulating evidence supports a taste component for free fatty acids in humans". Physiology & Behavior. 104 (4): 624–31. doi:10.1016/j.physbeh.2011.05.002. PMC 3139746. PMID 21557960.
  4. ↑ Liu P, Shah BP, Croasdell S, Gilbertson TA (June 2011). "Transient receptor potential channel type M5 is essential for fat taste". The Journal of Neuroscience. 31 (23): 8634–42. doi:10.1523/JNEUROSCI.6273-10.2011. PMC 3125678. PMID 21653867.
  5. ↑ Chaudhari N, Roper SD (August 2010). "The cell biology of taste". The Journal of Cell Biology. 190 (3): 285–96. doi:10.1083/jcb.201003144. PMC 2922655. PMID 20696704.
  6. ↑ Colsoul B, Schraenen A, Lemaire K, Quintens R, Van Lommel L, Segal A, Owsianik G, Talavera K, Voets T, Margolskee RF, Kokrashvili Z, Gilon P, Nilius B, Schuit FC, Vennekens R (March 2010). "Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice". Proceedings of the National Academy of Sciences of the United States of America. 107 (11): 5208–13. doi:10.1073/pnas.0913107107. PMC 2841940. PMID 20194741.
  7. ↑ 7.0 7.1 Philippaert K, Pironet A, Mesuere M, Sones W, Vermeiren L, Kerselaers S, Pinto S, Segal A, Antoine N, Gysemans C, Laureys J, Lemaire K, Gilon P, Cuypers E, Tytgat J, Mathieu C, Schuit F, Rorsman P, Talavera K, Voets T, Vennekens R (March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. doi:10.1038/ncomms14733. PMC 5380970. PMID 28361903.
  8. ↑ Kaske S, Krasteva G, König P, Kummer W, Hofmann T, Gudermann T, Chubanov V (July 2007). "TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells". BMC Neuroscience. 8: 49. doi:10.1186/1471-2202-8-49. PMC 1931605. PMID 17610722.
  9. ↑ Philippaert, Koenraad; Vennekens, Rudi (1 January 2015). "Chapter 19 - Transient Receptor Potential (TRP) Cation Channels in Diabetes". TRP Channels as Therapeutic Targets. Academic Press: 343–363. doi:10.1016/B978-0-12-420024-1.00019-9.
  10. ↑ 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. PMID 26501253.
  11. ↑ 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. PMID 21158685.
  12. ↑ Philippaert K, Kerselaers S, Voets T, Vennekens R (January 2018). "2+-Activated Monovalent Cation-Selective Channels". SLAS Discovery: 2472555217748932. doi:10.1177/2472555217748932. PMID 29316407.
  13. ↑ 13.0 13.1 Ullrich 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. PMID 15670874.
  14. ↑ 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. PMID 24452633.

Further reading

External links

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