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.