抄録
We studied the effects of protease inhibitors on 125I-fibrinogen binding to gel-filtrated platelets stimulated with ADP or epinephrine. Soybean trypsin inhibitor and leupeptin had no effect on fibrinogen binding to ADP- or epinephrine-stimulated platelets. Whereas phenylmethylsulfonyl fluoride (PMSF) inhibited the binding by 22-31%. Gabexate mesilate, p-guanidinobenzoate derivative, suppressed the binding by 11%, but was required to be added prior to the addition of agonists. Nafamostat mesilate, which has both guanidinobenzoate and amidinonaphtol in its structure, suppressed the fibrinogen binding dose-dependently, but also displaced the bound fibrinogen from ADP-stimulated platelets, that resulted in disaggregation. Scatchard analysis demonstrated that nafamostat mesilate decreased not only the number but also the affinity of the exposed fibrinogen receptors.
The fibrinogen binding to stimulated platelets was inhibited by serine protease inhibitors such as PMSF, gabexate mesilate and nafamost mesilate. It seems that the inhibitory effect of these agents on arachidonic acid release from platelet membrane resulted in prevention of exposure of fibrinogen receptors. Because it has been reported that aspirin and indomethacin decreased the exposure of fibrinogen binding sites of ADP-stimulated platelets. Nafamostat mesilate decreased, moreover, the affinity of the exposed fibrinogen receptor, that is, this agent might act antagonistically to fibrinogen receptors, glycoprotein IIb-IIIa.