ADP and platelet activation. Platelet activation by potent agonists such as thrombin or collagen causes the release of secondary agonists such as thromboxane A2 (TxA2) and the secretion of ADP from platelet dense granules. Platelet responses to ADP require the coordinate activation of two G protein–coupled receptors, P2Y1 and P2Y12, whose actions are described in the text. Drugs such as Ticlopidine and Clopidogrel block activation of P2Y12. Mechanisms that place a limit on unwarranted platelet activation include CD39 on the surface of endothelial cells, which hydrolyzes ADP to AMP, and PGI2 and NO, which increase the concentration of cAMP and cGMP within platelets.