Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets

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Abstract

Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50–75 μg/ml) through the lung or spleen specifically inhibits thromboxane A2 production and diverts the pathway to the prostaglandins, mainly prostaglandin F. In human platelets imidazole causes a dose-dependent inhibition of thromboxane A2 formation (ID50 5.5 × 10−4 M). This inhibition is accompanied by a dose-dependent increase in prostaglandin F. Since thromboxane A2 induces platelet aggregation and is a potent vasoconstrictor, diversion of pathways to prostaglandins with opposite or less potent actions might be of relevance in the treatment of cardiovascular diseases.

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    Present address: Rudolf Magnus Institute for Pharmacology, University of Utrecht, Vondellaan 6, Utrecht, The Netherlands.

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