Thrombin-induced lysosomal exocytosis in human platelets is dependent on secondary activation by ADP and regulated by endothelial-derived substances

Notably, lysosomal exocytosis in response to thrombin was significantly reduced if the secondary activation by ADP was inhibited by the P2Y 12 antagonist cangrelor, while inhibition of thromboxane A 2 formation by treatment with acetylsalicylic acid was of minor importance in this regard. Moreover, the NO-releasing drug S -nitroso- N -acetyl penicillamine (SNAP) or the cyclic AMP-elevating eicosanoid prostaglandin I 2 (PGI 2 ) significantly suppressed lysosomal exocytosis.

We conclude that platelet inhibitors that mimic functional endothelium such as PGI 2 or NO efficiently counteract lysosomal exocytosis. Furthermore, we suggest that secondary release of ADP and concomitant signaling via PAR1/4- and P2Y 12 receptors is important for efficient platelet lysosomal exocytosis by thrombin.