Functional interaction between purinergic receptors: Effect of ligands for A 2A and P2Y 12 receptors on P2Y 1 receptor function

摘要

A 2A adenosine receptor (A 2AR), P2Y 1 receptor (P2Y 1R) and P2Y 12 receptor (P2Y 12R) 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 Ca 2+ signaling evoked by the P2Y 1R agonist, 2-methylthioladenosine 5' diphosphate (2MeSADP) was significantly inhibited by the A 2AR antagonist (ZM241385 and SCH442416) and the P2Y 12R antagonist (ARC69931MX) using HEK293T cells expressing the three receptors. It was confirmed that inhibition of P2Y 1R signaling by A 2AR and P2Y 12R antagonists was indeed mediated through A 2AR and P2Y 12R 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.