ADP-INDUCED PLATELET ACTIVATION

Authors
Citation
Rn. Puri et Rw. Colman, ADP-INDUCED PLATELET ACTIVATION, Critical reviews in biochemistry and molecular biology, 32(6), 1997, pp. 437-502
Citations number
309
Categorie Soggetti
Biology
ISSN journal
10409238
Volume
32
Issue
6
Year of publication
1997
Pages
437 - 502
Database
ISI
SICI code
1040-9238(1997)32:6<437:APA>2.0.ZU;2-W
Abstract
Platelet activation is central to the pathogenesis of hemostasis and a rterial thrombosis. Platelet aggregation plays a major role in acute c oronary artery diseases, myocardial infarction, unstable angina, and s troke. ADP is the first known and an important agonist for platelet ag gregation. ADP not only causes primary aggregation of platelets but is also responsible for the secondary aggregation induced by ADP and oth er agonists. ADP also induces platelet shape change, secretion from st orage granules, influx and intracellular mobilization of Ca2+, and inh ibition of stimulated adenylyl cyclase activity. The ADP-receptor prot ein mediating ADP-induced platelet responses has neither been purified nor cloned. Therefore, signal transduction mechanisms underlying ADP- induced platelet responses either remain uncertain or less well unders tood. Recent contributions from chemists, biochemists, cell biologists , pharmacologists, molecular biologists, and clinical investigators ha ve added considerably to and enhanced our knowledge of ADP-induced pla telet responses. Although considerable efforts have been directed towa rd identifying and cloning the ADP-receptor, these have not been compl etely successful or without controversy. Considerable progress has bee n made toward understanding the mechanisms of ADP-induced platelet res ponses but disagreements persist. New drugs that do not mimic ADP have been found to inhibit fairly selectively ADP-induced platelet activat ion ex vivo. Drugs that mimic ADP and selectively act at the platelet ADP-receptor have been designed, synthesized, and evaluated for their therapeutic efficacy to block selectively ADP-induced platelet respons es. This review examines in detail the developments that have taken pl ace to identify the ADP-receptor protein and to better understand mech anisms underlying ADP-induced platelet responses to develop strategies for designing innovative drugs that block ADP-induced platelet respon ses by acting selectively at the ADP-receptor and/or by selectively in terfering with components of ADP-induced platelet activation mechanism s.