Isolation and Structure of Two Prostaglandin Endoperoxides That Cause Platelet Aggregation

Abstract

Incubation for a short time of arachidonic acid with the microsomal fraction of a homogenate of the vesicular gland of sheep in the presence of 1 mM p -mercuribenzoate followed by extraction and silicic acid chromatography yielded two prostaglandin endoperoxides. The structures of these compounds, i.e., 15-hydroperoxy-9α,11α-peroxidoprosta-5,13-dienoic acid (prostaglandin G 2 ) and 15-hydroxy-9α,11α-peroxidoprosta-5,13-dienoic acid (prostaglandin H 2 ), were assigned mainly by a number of chemical transformations into previously known prostaglandins. The new prostaglandins were 50-200 times (prostaglandin G 2 ) and 100-450 times (prostaglandin H 2 ) more active than prostaglandin E 2 on the superfused aorta strip. The half-life of the prostaglandin endoperoxides in aqueous medium (about 5 min) was significantly longer than that of “rabbit aorta-contracting substance” released from guinea pig lung, indicating that none of the prostaglandin endoperoxides is identical with this factor. Addition of 10-300 ng/ml of the endoperoxides to suspensions of washed human platelets resulted in rapid aggregation. Furthermore, platelet aggregation induced by thrombin was accompanied by release of material reducible by stannous chloride into prostaglandin F 2α , thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation.