Platelet prostaglandin production and its implications.
Both aspirin and indomethacin abolish platelet shape change and aggregation induced by arachidonic acid, indicating that these effects are due to prostaglandin production. An unstable prostaglandin endoperoxide (PGG2 or PGH2) is probably the mediator of the arachidonic acid effects, and they can be mimicked by the stable synthetic prostaglandin, 11-deoxy-15-methyl-15RS-PGE2 (Wy-17, 186). All three of these prostaglandins induce platelet aggregation in the presence of aspirin. Neither aspirin nor indomethacin inhibits shape change or primary aggregation induced by ADP, which indicates that these effects are not due to prostaglandin production. Arachidonic acid, Wy-17, 186, and ADP require fibrinogen as a cofactor in order to aggregate washed human platelets. However, the combination of ADP and arachidonic acid or of ADP and Wy-17, 186 is synergistic and will aggregate washed human platelets in the absence of added fibrinogen. No synergism is observed between arachidonic acnd and Wy-17, 186. During platelet degranulation (i.e., the platelet-release reaction) induced by collagen both ADP and prostaglandin endoperoxides are made available, and collagen can induce the aggregation of washed human platelets in the absence of added fibrinogen. Prostaglandin endoperoxides, ADP, and fibrinogen probably act in concert to aggregate platelets in normal hemostasis since the absence of any one of these principles usually has an effect on the bleeding time.
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009940:Organoids / Q000378:metabolism; D010545:Peroxides; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000097:blood*; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D010545:Peroxides; D011453:Prostaglandins; D011458:Prostaglandins E; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D007213:Indomethacin