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

British Journal of Haematology - Tập 91 Số 2 - Trang 434-444 - 1995
Christian Gachet1, Marco Cattaneo2, Philippe Ohlmann1, Béatrice Hechler1, Anna Lecchi2, Jérôme Chevalier1, Dominique Cassel1, Pier Mannuccio Mannucci2, Jean‐Pierre Cazenave1
1INSERM U.311, Biologie et Pharmacologic des Interactions du Sang avec les Vaisseaux et les Biomatériaux, Etablissement de Transfusion Sanguine de Strasbourg, Strasbourg, France
2A. Bianchi Bonomi Hemophilia and Thrombosis Centre, IRCCS Maggiore Hospital, University of Milano, Milano, Italy

Tóm tắt

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 Ca2+ influx. Binding studies, using the non‐ hydrolysable ligand [33P]2MeSADP, have shown that human platelets contain about 600 high‐affinity binding sites for 2MeSADP (Kd∼ 5 niw). These sites present pharmacological characteristics of a P2T 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 [33P]2MeSADP binding sites.The current data thus strongly suggest the presence of two ADP receptors, one responsible for shape change and rapid Ca2+ influx and the other a Gi protein‐coupled receptor responsible for Ca2+ mobilization from internal stores, inhibition of adenylyl cyclase and platelet aggregation.

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British Journal of Haematology

Tập 91 Số 2

434-444

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