No requirement of P2X1 purinoceptors for platelet aggregation

ADP produces a series of responses in rabbit platelets such as shape changes, aggregation and intracellular Ca2+ mobilization. In human platelets, the P2X1 receptor mediates a rapid increase in intracellular Ca2+ concentration ([Ca2+]i) upon stimulation with ADP. We investigated whether this phenomenon is also present in rabbit platelets. We found that the P2X1 receptor-mediated response was absent because there was (1) no elevation of [Ca2+]i in response to alpha,beta-methylene-ATP, a selective P2X1 receptor agonist, in fura-2-loaded platelets; (2) no change in the ADP-induced [Ca2+]i increase and platelet aggregation after P2X1 receptor desensitization with alpha,beta-methylene-ATP; (3) complete inhibition of the ADP-induced [Ca2+]i elevation by the P2Y1 receptor specific antagonist, A3'P5'PS, with a similar ID50 value both in the presence and absence of external Ca2+. These results indicate that ADP-induced [Ca2+]i elevation is mainly mediated by P2Y1 receptors in rabbit platelets. We conclude that the P2X1 receptor does not play a significant role in the ADP-induced platelet shape changes and aggregation.