Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2281-2285
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© 1999 American Heart Association, Inc.
Brief Review |
ADP Receptors and Clinical Bleeding Disorders
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.
Correspondence to Marco Cattaneo, MD, Hemophilia and Thrombosis Center, University of Milano, Via Pace 9, 20122 Milano, Italy. E-mail marco.cattaneo{at}unimi.it
Abstract—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
i2,
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.
Key Words: adenosine diphosphate • purino receptors • platelets • bleeding disorders • thrombosis
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