Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor.

ABSTRACT: Ticagrelor is a potent antagonist of the P2Y₁₂ receptor (P2Y₁₂R) and consequently an inhibitor of platelet activity effective in the treatment of atherothrombosis. Here, we sought to further characterize its molecular mechanism of action. Initial studies showed that ticagrelor promoted a greater inhibition of adenosine 5'-diphosphate (ADP)-induced Ca²⁺ release in washed platelets vs other P2Y₁₂R antagonists. This additional effect of ticagrelor beyond P2Y₁₂R antagonism was in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of G_s-coupled adenosine A_2A receptors. This contributed to an inc

SUBMITTER: Aungraheeta R 

PROVIDER: S-EPMC5161012 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature