Isolation and Structure of Two Prostaglandin Endoperoxides That Cause

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 mlMl p-mer- curibenzoate followed by extraction and silicic acid chromatography yielded two prostaglandin endoper- oxides. The structures of these compounds, i.e., 15-hy- droperoxy-9a ,lla-peroxidoprosta-5,13-dienoic acid (pros- taglandin G2) and 15-hydroxy-9a,lla-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 (prosta- glandin H2) more active than prostaglandin E2 on the super- fused aorta strip. The half-life of the prostaglandin endo- peroxides in aqueous medium (about 5 min) was signifi- cantly longer than that of "rabbit aorta-contracting sub- stance" 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 in- duced by thrombin was accompanied by release of ma- terial reducible by stannous chloride into prostaglandin F2a, thus indicating the involvement of endogenous prostaglandin endoperoxides in platelet aggregation. Direct evidence for the formation of an endoperoxide during prostaglandin (PG) biosynthesis was recently obtained (1).