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Purinoceptors on blood platelets: further pharmacological and clinical evidence to suggest the presence of two ADP receptors

1995; Wiley; Volume: 91; Issue: 2 Linguagem: Inglês

10.1111/j.1365-2141.1995.tb05319.x

1365-2141

Christian Gachet, Marco Cattaneo, Philippe Ohlmann, Béatrice Hechler, Anna Lecchi, Jérôme Chevalier, Dominique Cassel, Pier Mannuccio Mannucci, Jean‐Pierre Cazenave,

Blood Coagulation and Thrombosis Mechanisms

Summary. Platelet aggregation by ADP plays a major role in the development and extension of arterial thrombosis. The antithrombotic thienopyridine compounds ticlopidine and clopidogrel have proved useful tools to investigate the mechanisms of ADP‐induced platelet activation. In essence, although clopidogrel has been shown to completely and selectively block ADP‐induced platelet aggregation, G protein activation and inhibition of adenylyl cyclase, this drug does not affect shape change and Ca 2+ influx. Binding studies, using the non‐ hydrolysable ligand [ 33 P]2MeSADP, have shown that human platelets contain about 600 high‐affinity binding sites for 2MeSADP (K d ∼ 5 niw). These sites present pharmacological characteristics of a P 2T receptor. Clopidogrel treatment reduces the number of sites by 70% on rat platelets (from 1200 to 450) and leaves the residual binding sites resistant to clopidogrel. Moreover, patients with congenital impairment of ADP‐induced platelet aggregation but normal shape change display very low levels of [ 33 P]2MeSADP binding sites.The current data thus strongly suggest the presence of two ADP receptors, one responsible for shape change and rapid Ca 2+ influx and the other a Gi protein‐coupled receptor responsible for Ca 2+ mobilization from internal stores, inhibition of adenylyl cyclase and platelet aggregation.