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Characteristics of an ADP receptor mediating platelet activation

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Summary

Adenosine diphosphate (ADP) is known to induce platelet shape change, aggregation and fibrinogen binding, followed by secretion. These processes are mediated by the binding of ADP to an externally oriented protein of the platelet plasma membrane. An affinity analog of ATP, a competitive inhibitor of the action of ADP, has been utilized to probe the structure and function of this receptor. FSBA (5′-p-fluorosulfonylbenzoyl adenosine) covalently modifies a single protein in intact platelets with Mr = 100 000 and concomitantly inhibits platelet shape change, aggregation and fibrinogen binding. Studies on platelet membranes demonstrate non-covalent association of ADP-binding protein with actin which is also labeled by FSBA but only in isolated membranes. This finding suggests a structural and functional coupling of the receptor to the contractile process. The putative ADP receptor covalently modified with FSBA is cleaved by chymotrypsin, a process that reverses the inability of the platelets to bind fibrinogen. Thus, the Mr = 100 000 polypeptide may be involved in the proteolytic exposure of fibrinogen binding sites on the platelet surface. The ability of FSBA to inhibit platelet aggregation and fibrinogen binding by prostaglandin H2 derivatives and epinephrine suggest that ADP is involved in these processes. However, the interaction is not at the receptor level since shape change, stimulated by PGH2 derivatives and yohimbine (epinephrine antagonist) binding are unaffected by FSBA. Finally, the action of ADP to inhibit PGE1- or PGI2-stimulated adenylate cyclase appears to be mediated by a receptor distinct for the protein modified by FSBA.

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Abbreviations

5′FSBA:

5′-p-fluorosulfonylbenzoyl adenosine

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Authors and Affiliations

  1. Thrombosis Research Center and Hematology Oncology Section of the Department of Medicine, Temple University School of Medicine, 19040, Philadelphia, PA, USA

    Robert W. Colman & William R. Figures

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  1. Robert W. Colman
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Colman, R.W., Figures, W.R. Characteristics of an ADP receptor mediating platelet activation. Mol Cell Biochem 59, 101–111 (1984). https://doi.org/10.1007/BF00231307

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