Cardiac human bitter taste receptors contain naturally occurring variants that alter function.

Bitter taste receptors (T2R) are a subfamily of G protein-coupled receptors that enable humans to detect aversive and toxic substances. The ability to discern bitter compounds varies between individuals and is attributed mainly to naturally occurring T2R polymorphisms. T2Rs are also expressed in numerous non-gustatory tissues, including the heart, indicating potential contributions to cardiovascular physiology. In this study. T2Rs that have previously been identified in human cardiac tissues (T2Rs - 10, 14, 30, 31, 46 and 50) and their naturally occurring polymorphisms were functionally characterised. The ligand-dependent signaling responses of some T2R variants were completely abolished (T2R30 Leu ²⁵² and T2R46 Met ²²⁸ ), whereas other receptor variants had moderate changes in their maximal response, but not potency, relative to wild type. Using a cAMP fluorescent biosensor, we reveal the productive coupling of T2R14, but not the T2R14 Phe ²⁰¹ variant, to endogenous Gα _i . Modeling revealed that these variants resulted in altered interactions that generally affected ligand binding (T2R30 Leu ²⁵² ) or Gα protein interactions (T2R46 Met ²²⁸ and T2R14 Phe ²⁰¹ ), rather than receptor structural stability. Interestingly, this study is the first to show a difference in signaling for T2R50 Tyr ²⁰³ (rs1376251) which has been associated with cardiovascular disease. The observation of naturally occurring functional variation in the T2Rs with the greatest expression in the heart is important, as their discovery should prove useful in deciphering the role of T2Rs within the cardiovascular system.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)