Inhibition of thromboxane synthetase by OKY-1581 stimulates the formation of PGE2, PGF2 alpha, PGD2 and 6-keto-PGF1 alpha in human platelets.
When intact human platelets were incubated with 200 microM 14C-arachidonic acid the formation of TXB2 and HHT was inhibited dose dependently by OKY-1581. The IC50 for the formation of TXB2 was 60 nM and for HHT 90 nM. The amounts of PGE2, PGF2 alpha, PGD2 and 6-keto- PGF1 alpha were correspondingly increased. The combined amount of all cyclo-oxygenase metabolites (TXB2, HHT and prostaglandins) was not changed by OKY-1581 (1 nM - 10 microM). The formation of the lipoxygenase metabolite, 12-HETE, was also not changed by OKY-1581. The present study indicates that the inhibition of thromboxane synthetase in human platelets will direct arachidonate metabolism via the cyclo-oxygenase pathway mainly to PGE2, PGF2 alpha and PGD2 and to a smaller extent to PGI2.
D000179:Acrylates / Q000494:pharmacology*; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D001095:Arachidonic Acids; D008689:Methacrylates; D011453:Prostaglandins; D016718:Arachidonic Acid; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010088:Oxidoreductases; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase