Synergistic inhibition of platelet activation by plasmin and prostaglandin I2.
Endothelial cell prostacyclin (PGI2) inhibits platelet activation by raising platelet cyclic AMP. Previously, platelet activation was also shown to be blocked by plasmin formed by endothelium-derived tissue plasminogen activator (TPA). We have now studied interactions between PGI2 and plasmin in the control of platelet function. PGI2 and plasmin cause synergistic inhibition of thrombin- and ADP-induced aggregation of washed platelets. Inhibition by PGI2 is similarly potentiated by TPA added to platelet-rich plasma to generate plasmin. Thrombin-stimulated rise in platelet cytosolic Ca2+, measured by fura2 fluorescence, and thromboxane A2 formation, measured by radioimmunoassay (RIA), are likewise synergistically inhibited by PGI2 and plasmin. Plasmin neither increases nor potentiates PGI2-stimulated increases in platelet cyclic AMP. Thus, PGI2 and plasmin cause synergistic inhibition of platelet activation by both cyclic AMP-dependent and independent mechanisms. This interaction between two different endothelium-derived products may play an important role in localizing the hemostatic plug to a site of vascular injury by preventing further thrombin-mediated accrual of platelets.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D011464:Epoprostenol / Q000494:pharmacology*; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D013917:Thrombin; D005341:Fibrinolysin; D002118:Calcium