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.