Functional interaction between purinergic receptors: effect of ligands for A2A and P2Y12 receptors on P2Y1 receptor function

AbstractA2A adenosine receptor (A2AR), P2Y1 receptor (P2Y1R) and P2Y12 receptor (P2Y12R) are predominantly expressed on human platelets. The individual role of each of these receptors in platelet aggregation has been actively reported. Previously, hetero-oligomerization between these three receptors has been shown to occur. Here, we show that Ca2+ signaling evoked by the P2Y1R agonist, 2-methylthioladenosine 5’ diphosphate (2MeSADP) was significantly inhibited by the A2AR antagonist (ZM241385 and SCH442416) and the P2Y12R antagonist (ARC69931MX) using HEK293T cells expressing the three receptors. It was confirmed that inhibition of P2Y1R signaling by A2AR and P2Y12R antagonists was indeed mediated through A2AR and P2Y12R using 1321N1 human astrocytoma cells which do not express P2Y receptors. We expect that intermolecular signal transduction and specific conformational changes occur among components of hetero-oligomers formed by these three receptors