Whilst the taste of acid and salty foods appear to be sensed by regulation of ion channel activity, bitter, sweet and umami tastes are sensed by specialised GPCR. Two classes of taste GPCR have been identified, T1R and T2R, which are similar in sequence and structure to Class C and Class A GPCR, respectively. Activation of taste receptors appears to involve gustducin- (Gαt3) and Gα14-mediated signalling, although the precise mechanisms remain obscure. Gene disruption studies suggest the involvement of PLCβ2 [5], TRPM5 [5] and IP3 [1] receptors in post-receptor signalling of taste receptors. Although predominantly associated with the oral cavity, taste receptors are also located elsewhere, including further down the gastrointestinal system, in the lungs and in the brain.

Sweet/Umami: T1R3 acts as an obligate partner in T1R1/T1R3 and T1R2/T1R3 heterodimers, which sense umami or sweet, respectively. T1R1/T1R3 heterodimers respond to L-glutamic acid and may be positively allosterically modulated by 5'-nucleoside monophosphates, such as 5'-GMP [2]. T1R2/T1R3 heterodimers respond to sugars, such as sucrose, and artificial sweeteners, such as saccharin [3].

Positive allosteric modulators of T1R2/T1R3 have been reported [4]. Such compounds enhance the sweet taste of sucrose mediated by these receptors, but are tasteless on their own.

* Key recommended reading is highlighted with an asterisk

* Behrens M, Ziegler F. (2020) Structure-Function Analyses of Human Bitter Taste Receptors-Where Do We Stand?. Molecules, 25 (19): 4423. [PMID:32993119]

* Palmer RK. (2019) A Pharmacological Perspective on the Study of Taste. Pharmacol Rev, 71 (1): 20-48. [PMID:30559245]

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2. Li X, Tomita M, Pilbeam CC, Breyer RM, Raisz LG. (2002) Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo. Prostaglandins Other Lipid Mediat, 67 (3-4): 173-80. [PMID:12013525]

3. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. (2001) Mammalian sweet taste receptors. Cell, 106 (3): 381-90. [PMID:11509186]

4. Yamada K, Nakazawa M, Matsumoto K, Tagami U, Hirokawa T, Homma K, Mori S, Matsumoto R, Saikawa W, Kitajima S. (2019) Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3. ACS Med Chem Lett, 10 (5): 800-805. DOI: 10.1021/acsmedchemlett.9b00051 [PMID:31098002]

5. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ. (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell, 112 (3): 293-301. [PMID:12581520]