Diverse signalling of the platelet P2Y1 receptor leads to a dichotomy in platelet function

Inhibition of PLC, but not Rac1 or RhoA, suppressed platelet aggregation induced by ADP and MRS2365. In contrast, platelet chemotaxis and PINC, were significantly attenuated by inhibition of platelet Rac1 or RhoA, but not PLC. MRS2365, compared to ADP had a less pronounced effect on P2Y1-induced aggregation, but a similar efficacy to stimulate platelet chemotaxis and PINC, which might be explained by differences in molecular interaction of ADP compared to MRS2365 with the P2Y1 receptor. Platelet P2Y1 receptor activation during inflammation signals through alternate pathways involving Rho GTPases in contrast to canonical P2Y1 receptor induced PLC signalling. This might be explained by selective molecular interactions of ligands within the orthosteric site of the P2Y1 receptor.