Differential long-term regulation of TAS2R14 by structurally distinct agonists.

ABSTRACT: Bitter taste receptor-14 (TAS2R14) is a GPCR also expressed on human airway smooth muscle cells, which signals to intracellular [Ca²⁺], resulting in relaxation of the airway, and is a novel target for bronchodilators. Here, we examine long-term, agonist-promoted down-regulation of TAS2R14 expression because tachyphylaxis would be an undesirable therapeutic characteristic. Five TAS2R structurally distinct full agonists were studied to ascertain biasing away from down-regulation. Agonist exposure for 18 h caused minimal desensitization by diphenhydramine (DPD) compared with ∼50% desensitization with all other agonists. Agonists evoked β-arrestin recruitment to TAS2R14, which was not seen with a phosphoacceptor-deficient mutant, TAS2R14-10A. All agonists except for DPD also caused

SUBMITTER: Woo JA 

PROVIDER: S-EPMC6902689 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature