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)

This article has been cited by other articles:

				T. Todaka, C. Yokoyama, H. Yanamoto, N. Hashimoto, I. Nagata, T. Tsukahara, S. Hara, T. Hatae, R. Morishita, M. Aoki, et al. Gene Transfer of Human Prostacyclin Synthase Prevents Neointimal Formation After Carotid Balloon Injury in Rats • Editorial Comment Stroke, February 1, 1999; 30(2): 419 - 426. [Abstract] [Full Text] [PDF]

				T. Hohlfeld, T.-P. Zucker, J. Meyer, and K. Schror Expression, Function, and Regulation of E-Type Prostaglandin Receptors (EP3) in the Nonischemic and Ischemic Pig Heart Circ. Res., November 19, 1997; 81(5): 765 - 773. [Abstract] [Full Text]

				C. J. Knight, M. Panesar, C. Wright, D. Clarke, P. S. Butowski, D. Patel, A. Patrineli, K. Fox, and A. H. Goodall Altered Platelet Function Detected by Flow Cytometry : Effects of Coronary Artery Disease and Age Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2044 - 2053. [Abstract] [Full Text]

				Y. Sasaki, T. Takahashi, I. Tanaka, K. Nakamura, Y. Okuno, O. Nakagawa, S. Narumiya, and K. Nakao Expression of Prostacyclin Receptor in Human Megakaryocytes Blood, August 1, 1997; 90(3): 1039 - 1046. [Abstract] [Full Text] [PDF]