Prostacyclin potentiates 13-azaprostanoic acid-induced platelet deaggregation.
The specific thromboxane A2/prostaglandin H2 (TXA2/PGH2) antagonist 13-azaprostanoic acid (13-APA) reverses platelet aggregation stimulated by TXA2/PGH2 and the prostaglandin endoperoxide analog U46619. The present report demonstrates that the deaggregatory properties of 13-APA are potentiated by prostacyclin (PGI2). Human platelet-rich plasma was aggregated with U46619. Deaggregation was induced 2 min subsequent to the addition of the aggregating agent. Concentrations of 13-APA or PGI2 which induced 20 percent deaggregation were determined. Simultaneous addition of half of these concentrations resulted in 60 percent deaggregation, demonstrating that the observed response was supraadditive. Measurement of cyclic adenosine 3':5' monophosphate (cAMP) in resting or deaggregating platelets demonstrated that 13-APA itself did not stimulate cAMP production nor did 13-APA facilitate PGI2-induced increases in cAMP. In separate studies PGI2 and 13-APA were added to PRP prior to the induction of aggregation by U46619. Under these conditions, additive inhibition of aggregation was observed. Thus, it is clear that the pharmacological interaction between PGI2 and 13-APA depends upon the relative state of platelet activation.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004357:Drug Synergism; D011464:Epoprostenol / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors*; D011453:Prostaglandins / Q000494:pharmacology*; D011466:Prostanoic Acids / Q000494:pharmacology*
D005227:Fatty Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011466:Prostanoic Acids; D000244:Adenosine Diphosphate; C022574:13-azaprostanoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D000242:Cyclic AMP