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.
Department of Surgery II, Osaka University Medical School, Japan.
M
M
Sakon
K
K
Murata
K
K
Fujitani
Y
Y
Yano
J
J
Kambayashi
Y
Y
Uemura
T
T
Kawasaki
E
E
Shiba
T
T
Mori
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D054645:Protein Phosphatase 1; D013917:Thrombin / Q000494:pharmacology*
D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D010980:Platelet Membrane Glycoproteins; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D013917:Thrombin