Activation of phospholipase C is dissociated from arachidonate metabolism during platelet shape change induced by thrombin or platelet-activating factor. Epinephrine does not induce phospholipase C activation or platelet shape change.
The present study compares the molecular mechanism by which thrombin, platelet-activating factor, and epinephrine induce platelet activation. Thrombin and platelet-activating factor induce an initial activation of phospholipase C, as measured by formation of 1,2-diacylglycerol and phosphatidic acid, during platelet shape change which is independent of and dissociated from metabolism of arachidonic acid. Phospholipase C activation and shape change are independent of extracellular Ca2+ and Mg2+. Formation of cyclooxygenase products occurs subsequent to the initial activation of phospholipase C and those metabolites are associated with platelet aggregation and further activation of phospholipase C. On the other hand, epinephrine is an unique platelet stimulus since it requires extracellular divalent cations and does not induce platelet shape change or activation of phospholipase C. Our results indicate that activation of phospholipase C may be a mechanism by which physiological agonists can activate platelets independently of extracellular divalent cations.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010740:Phospholipases / Q000097:blood*; D010972:Platelet Activating Factor / Q000502:physiology*; D010974:Platelet Aggregation; D013917:Thrombin / Q000502:physiology*; D014268:Trifluoperazine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood*
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D014268:Trifluoperazine; D016718:Arachidonic Acid; D010740:Phospholipases; D010738:Type C Phospholipases; D013917:Thrombin; D001241:Aspirin; D007213:Indomethacin; D004837:Epinephrine