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Purinoceptors on blood platelets: further pharmacological and clinical evidence to suggest the presence of two ADP receptors
Author(s) -
Gachet Christian,
Cattaneo Marco,
Ohlmann Philippe,
Hechler Béatrice,
Lecchi Anna,
Chevalier Jérôme,
Cassel Dominique,
Mannucci Pier Mannuccio,
Cazenave JeanPierre
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05319.x
Subject(s) - platelet , adenylyl cyclase , clopidogrel , chemistry , ticlopidine , receptor , adenosine diphosphate , thienopyridine , p2y12 , platelet activation , pharmacology , medicine , biochemistry , biophysics , endocrinology , platelet aggregation , biology , aspirin
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.