Gradient-dependent inhibition of stimulatory signaling from platelet G protein-coupled receptors.

ABSTRACT: As platelet activation is an irreversible and potentially harmful event, platelet stimulatory signaling must be tightly regulated to ensure the filtering-out of inconsequential fluctuations of agonist concentrations in the vascular milieu. Herein, we show that platelet activation via G protein-coupled receptors is gradient-dependent, i.e., determined not only by agonist concentrations per se but also by how rapidly concentrations change over time. We demonstrate that gradient-dependent inhibition is a common feature of all major platelet stimulatory G protein-coupled receptors, while platelet activation via the non-G protein-coupled receptor glycoprotein VI is strictly concentration-dependent. By systematically characterizing the effects of variations in temporal agonist concentrati

SUBMITTER: Macwan AS 

PROVIDER: S-EPMC6601095 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature