ADP Receptors and Clinical Bleeding Disorders

Cattaneo, Marco
Gachet, Christian

From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (M.C.), IRCCS Ospedale Maggiore, University of Milano, Milano, Italy, and INSERM U.311 (C.G.), Etablissement de Transfusion Sanguine de Strasbourg, Strasbourg, France.

Received February 8, 1999; revision accepted March 11, 1999.

Correspondence to Marco Cattaneo, MD, Hemophilia and Thrombosis Center, University of Milano, Via Pace 9, 20122 Milano, Italy. E-mail [email protected]

Arteriosclerosis, Thrombosis, & Vascular Biology 19(10):p 2281-2285, October 1999.

ADP plays a key role in hemostasis and thrombosis. Despite its early identification in 1961 as the first known aggregating agent, the molecular basis of ADP-induced platelet activation is only beginning to be understood. The present review proposes a model of 3 purinergic receptors contributing separately to the complex process of ADP-induced platelet aggregation: the P2X₁ ionotropic receptor, responsible for rapid influx of ionized calcium into the cytosol; the P2Y₁ metabotropic receptor, responsible for mobilization of ionized calcium from internal stores, which initiates aggregation; and an as-yet-unidentified P2Y receptor coupled to G_αi2, which is essential for the full aggregation response to ADP. It is probable that this as-yet-unidentified receptor is the molecular target of the ADP-selective antiaggregating drugs ticlopidine and clopidogrel. In addition, it is probably defective in patients with a bleeding diathesis that is characterized by selective impairment of platelet responses to ADP.