Inhibition of platelet aggregation and elevation of cyclic-AMP levels in platelets by 13,14-dehydro PGI2 methyl ester.

13,14-Dehydro PGI2 (dh-PGI2) and 13,14-dehydro PGI2 methyl ester (dh-PGI2-Me) inhibited platelet aggregation and release of [14C]-serotonin and ADP induced by collagen, ADP, arachidonic acid and PGG2. The inhibitory dose (ID50) ofg dh-PGI2-Me on platelet aggregation was 3 x 10(-9)M when induced with collagen, 2 x 10(-8) M with ADP, 5 x 10(-9) M with arachidonic acid and 1 x 10(-8)M with PGG2. The effects of dh-PGI2 and dh-POGI2-Me on platelet aggregation appear to be mediated by cyclic AMP, since both agents were potent to stimulate platelet cyclic AMP formation. In this respect dh-PGI2-Me was more effective than dh-PGI2 and PGE1. The actions of dh-PGI2-Me on platelet aggregation reported in this study suggest that is posseses similar biological properties as natural PGI2. Since dh-PGI2-Me is considerably more stable at physiological pH than PGI2 (Fried, J. and Barton, J. (1977) Proc. Natl. Acad. Sci. USA, 74, 2199-2203) this PGI2 analog might be useful as an anti-thrombotic drug.