Purinoceptors and platelet aggregation

1 Adenosine 5'-diphosphate (ADP) is a physiologically important mediator, being released from damaged cells and from aggregating platelets. It acts on platelets to cause aggregation via a purinoceptor ('P-2T-purinoceptor') at which adenosine 5'-triphosphate (ATP) is a competitive antagonist; however, the way in which it does so is not fully understood. 2 ADP activates a G(i2) protein, is a weak activator of phospholipase C but causes calcium mobilization from internal stores, and also inhibits adenylate cyclase. It seems likely that these effects are mediated by a single receptor but this is still unclear. 3 ADP also causes a rapid calcium influx which has the characteristics of a receptor-operated channel, and it has been suggested that this is due to a P-2X1 receptor. This suggests the presence of at least two types of receptor responding to ADP, one G protein coupled and one a cation channel, and raises questions about the role of ATP in platelet function. 4 Adenosine acts via an A(2a) receptor to stimulate adenylate cyclase in platelets, and this nonselectively inhibits platelet activation. As ADP released from platelets is broken down to adenosine by ectonucleotidases on endothelial cells, this may provide an important mechanism for limiting inappropriate platelet aggregation in an intact blood vessel.