Differential involvement of the P2Y(1) and P2Y(T) receptors in the morphological changes of platelet aggregation

The relative contributions of the P2Y(1) and P2Y(T) receptors to the morpho logical changes induced in platelets by ADP or ADP-releasing agonists were assessed using two P2 antagonists, A2P5P add AR-C67085, selective for P2Y(1 ) and P2Y(T), respectively. The P2Y(1) receptor was found to be involved in i) the centralization of secretory granules elicited by ADP, ii) the forma tion of filopodia induced by released ADP in weakly activated platelets and iii) actin polymerization and the cytoskeletal translocation of cdc42, rac 1 and rhoA, in an integrin alpha (IIb)beta (3) dependent manner, in ADP-sti mulated platelets. In contrast: the P2Y(T) receptor was shown i) to be esse ntial for the formation of stable macroaggregates, ii) to enhance actin pol ymerization and the cytoskeletal translocation of small GTPases, probably t hrough amplification of platelet aggregation, and iii) not to be involved i n the early steps of platelet activation since its blockade did not affect the cytoskeletal translocation of rhoA.