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.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta; D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism
D011453:Prostaglandins; D012701:Serotonin; D000244:Adenosine Diphosphate; C026435:13,14-dehydroprostaglandin I2 methyl ester; C026434:13,14-dehydroprostaglandin I2; D011464:Epoprostenol; D000242:Cyclic AMP