Abstract
We investigated the relationship between ristoc etin-induced platelet agglutination (RIPA) and glycoprotein (GP) lib/Ilia. Aspirin, diltiazem, prostaglandin E1 caused disagglutination of RIPA, whereas an ADP scavenger or protein kinase C inhibitors did not. Monoclonal anti-GPIIb/IIIa and anti-GPIIIa antibodies, RGDS, or RGD caused disagglutination of RIPA, but not monoclonal anti-GPIIb antibody or HHLGGAKQAGDV. Binding of von Willebrand factor (vWf) to platelets increased 5 sec after ristocetin addition, but not that of fibrinogen (Fbg), fibronectin (FN), or thrombospondin (TSP). Binding of the latter 3 proteins to aspirin-treated platelets did not increase 15 min after ristocetin addition, but their binding to platelets incubated with RGDS increased 15 min after ristocetin addition. These results suggest that vWf binding to GPIb causes an increase of [Ca2±]i via thromboxane A2 synthesis, along with activation GPIIIa but not protein kinase C. Irreversible and full RIPA involves vWf binding to both GPIb and activated GPIIIa.
