CALYCULIN-A INHIBITS THE EXPOSURE OF FIBRINOGEN RECEPTOR IN THROMBIN-STIMULATED PLATELETS

Calyculin A (CLA) and okadaic acid (OA), specific and potent inhibitors of protein phosphatase 1/2A, inhibit platelet aggregation. However, their inhibitory mechanisms remain unknown. We investigated the effects of CLA on the exposure of fibrinogen receptor in thrombin-stimulated platelets, using flow cytometry with a monoclonal antibody against the fibrinogen receptor of activated glycoprotein (Gp)IIb/IIIa complex (PAC−1). CLA inhibited the exposure of fibrinogen receptor in a dose related manner when added either before or 3 min after thrombin stimulation. In contrast, CLA had no significant effect when the expression of GpIIb/IIIa complex was examined in resting platelets, using a monoclonal antibody recognizing non-activated GpIIb/IIIa complex (NNKY1−32). These results suggest that protein phosphatase 1/2A may be directly involved in the exposure of platelet fibrinogen receptor. © 1993 Academic Press, Inc.