Prostaglandins and human platelet aggregation. Implications for the anti-aggregating activity of thromboxane-synthase inhibitors.
Selective pharmacological blockade of thromboxane-synthase in human platelets by dazoxiben resulted in the reorientation of cyclic-endoperoxides towards PGE2, PGD2 and PGF2 alpha. At concentrations which can be reached when thromboxane-synthase is inhibited, PGE2 (100-500 nM) exerted a marked, concentration-dependent pro-aggregatory effect. This required the formation of endogenous or the addition of exogenous endoperoxides and was prevented by PGD2 or 13-aza-prostanoic acid, a selective antagonist of PGH2/TxA2 receptors. The anti-aggregating effect of PGD2 was evident at concentrations lower than those obtained in dazoxiben-treated platelets. It is proposed that in the absence of TxA2 generation, a combination of endoperoxides and PGE2 may result in normal aggregation. The latter may be inhibited by PGD2. No interference of PGF2 alpha on platelet function could be shown.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D015237:Dinoprost; D015232:Dinoprostone; D004357:Drug Synergism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D015230:Prostaglandin D2; D011449:Prostaglandin Endoperoxides / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011457:Prostaglandins D / Q000378:metabolism / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D011460:Prostaglandins F / Q000378:metabolism / Q000494:pharmacology; D011466:Prostanoic Acids / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011466:Prostanoic Acids; C029166:dazoxiben; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C022574:13-azaprostanoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; D001241:Aspirin; D015230:Prostaglandin D2