Functional interaction between purinergic receptors: Effect of ligands for A _2A and P2Y ₁₂ receptors on P2Y ₁ receptor function

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.