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 G2) and 15-hydroxy-9α,11α-peroxidoprosta-5,13-dienoic acid (prostaglandin H2), were assigned mainly by a number of chemical transformations into previously known prostaglandins. The new prostaglandins were 50-200 times (prostaglandin G2) and 100-450 times (prostaglandin H2) more active than prostaglandin E2 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 F2α, thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation.
