Platelet prostacyclin binding in coronary artery disease.
Reduced responsiveness of platelets to prostacyclin, reported in vitro in patients with coronary artery disease, has been thought to be a factor predisposing toward coronary thrombosis and vasospasm as a result of enhanced in vivo release of cyclic endoperoxides and thromboxane A2 by the platelets. In this study, specific binding of prostacyclin to intact platelets was determined in patients with coronary artery disease by direct binding studies using 9-3H-prostacyclin sodium salt. In addition, the inhibitory effect of prostacyclin on primary aggregation induced by adenosine diphosphate and cyclic adenosine monophosphate (cyclic AMP) accumulation stimulated by prostacyclin was examined. Twenty patients with angiographically documented coronary artery disease and stable angina, 8 patients with acute myocardial infarction, 14 healthy volunteers and 10 patients with normal angiograms were studied. In patients with stable angina, binding capacity and affinity of platelet prostacyclin binding sites and prostacyclin-induced cyclic AMP accumulation were not different from those of control subjects. In patients with acute myocardial infarction, however, binding capacity of platelet prostacyclin receptors was significantly reduced (0.69 +/- 0.45 versus 1.35 +/- 0.37 pmol/10(9) platelets, p = 0.001) and the postreceptor response, represented by platelet responsiveness to prostacyclin and prostacyclin-induced cyclic AMP synthesis, was impaired. Because all patients with myocardial infarction were receiving intravenous heparin and nitroglycerin, which might interfere with platelet prostacyclin binding, competition experiments were performed in vitro. Neither heparin (3 to 250 IU/ml) nor nitroglycerin (0.8 to 22 microM) displaced specifically bound 9-3H-prostacyclin. L-Epinephrine in concentrations up to 10 microM also exhibited no competition with specific platelet prostacyclin binding.(ABSTRACT TRUNCATED AT 250 WORDS)
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000787:Angina Pectoris / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood*; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000097:blood*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D005996:Nitroglycerin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000378:metabolism
D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D000244:Adenosine Diphosphate; D006493:Heparin; D011464:Epoprostenol; D000242:Cyclic AMP; D005996:Nitroglycerin