Asialo von Willebrand factor binding to and aggregation of platelets: effects of inhibitors of platelet metabolism and function.
Asialo von Willebrand factor (As-VWF) binds both to the glycoprotein lb (GPlb) and glycoprotein llb-llla (GPllb-llla) complex. We studied the role of various platelet pathways involved in the As-VWF-induced platelet aggregation. We used prostacyclin, dibutyryl cyclic adenosine monophosphate, forskolin, 5'-p-fluorosulfonyl adenosine, apyrase, aspirin, and EDTA to evaluate the role of adenosine diphosphate (ADP), thromboxane synthesis, and the effects of calcium on the binding of As-VWF to platelets and ensuing aggregation. We found that agents that increase intracellular cyclic adenosine monophosphate totally inhibit As-VWF-induced platelet aggregation but only partially inhibit the As-VWF binding to the GPllb-llla complex. The endoperoxide-thromboxane pathway does not play a major role in either As-VWF binding to platelets or induction of platelet aggregation. As-VWF binding to the GPllb-llla complex appears to be approximately 70% to 80% ADP dependent and approximately 20% to 30% ADP independent. The binding of As-VWF to the GPllb-llla complex appears to be different from the binding of intact VWF or fibrinogen to the GPllb-llla complex with the platelet agonists ADP or thrombin.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001212:Asialoglycoproteins; D001241:Aspirin / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D014841:von Willebrand Factor / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001212:Asialoglycoproteins; D010980:Platelet Membrane Glycoproteins; C044131:asialo-von Willebrand Factor; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001241:Aspirin; D015056:1-Methyl-3-isobutylxanthine