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=== Downstream signaling === ==== TAS1R1 + TAS1R3 ==== The TAS1R1 + TAS1R3 receptor is a [[G protein-couple receptor]], much like the sweet and bitter receptors. It uses the same downstream signaling molecules, including [[G beta-gamma complex|G proteins beta-gamma]], [[PLCB2]] and [[Inositol triphosphate|IP<sub>3</sub>]], to ultimately cause a release of [[calcium]] (Ca<sup>2+</sup>) from intracellular stores.<ref name=Kinnamon>{{cite journal | author = Kinnamon SC | title = Taste receptor signalling β from tongues to lungs | journal = Acta Physiologica | volume = 204 | issue = 2 | pages = 158β68 | date = February 2012 | pmid = 21481196 | pmc = 3704337 | doi = 10.1111/j.1748-1716.2011.02308.x}}</ref> Calcium activates a so-called transient-receptor-potential cation channel [[TRPM5]] that leads to membrane [[depolarization]] and the consequent release of [[Adenosine triphosphate|ATP]] across a channel of [[CALHM1]] and [[CALHM3]].<ref name=Diepeveen>{{cite journal |last1=Diepeveen |first1=J |last2=Moerdijk-Poortvliet |first2=TCW |last3=van der Leij |first3=FR |title=Molecular insights into human taste perception and umami tastants: A review. |journal=Journal of Food Science |date=April 2022 |volume=87 |issue=4 |pages=1449β1465 |doi=10.1111/1750-3841.16101 |pmid=35301715|pmc=9314127 }}</ref> The ATP released by the "Type II" cell is detected by P2X receptors on nearby afferent gustatory nerve fibers and P2Y receptors on adjacent taste cells. P2X appears to be indispensable for the transduction of umami, so this is probably the main route for umami signals.<ref name=Kinnamon/> "Type III" cells, which directly connect to the nerve synapses, also respond to the released ATP by releasing neurotransmitters. One of these neurotransmitters, [[serotonin]], regulates the release of ATP by the type II cells.<ref name=Kinnamon/> ==== mGluR1 and mGluR4 ==== Signal from these two receptors are conveyed in a manner independent of TRPM5. Single umami-sensitive fibres in mice are mostly either "sucrose-best" or "glutamate-best". Within each type there are two subtypes: one shows synergistic activation between monopotassium glutamate and inosine monophosphate, the other does not. The TAS1R1/3 + TRPM5 route uses the "sucrose-best" fibers with synergy, while mGluR1 and mGluR4 use both of the "glutamate-best" subtypes.<ref>{{cite journal |last1=Yasumatsu |first1=Keiko |last2=Ogiwara |first2=Yoko |last3=Takai |first3=Shingo |last4=Yoshida |first4=Ryusuke |last5=Iwatsuki |first5=Ken |last6=Torii |first6=Kunio |last7=Margolskee |first7=Robert F. |last8=Ninomiya |first8=Yuzo |title=Umami taste in mice uses multiple receptors and transduction pathways |journal=The Journal of Physiology |date=March 2012 |volume=590 |issue=5 |pages=1155β1170 |doi=10.1113/jphysiol.2011.211920 |pmid=22183726|pmc=3381822 }}</ref>
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