1989 Volume 20 Issue 6 Pages 553-559
We have recently reported that nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited the binding of fibrinogen to ADP-stimulated human platelets in an antagonistic manner. In respect to the similar effect of FUT-175 to ArgGly-Asp-Ser (RGDS), synthetic peptide constituted cell attachment domain of fibronectin, on fibrinogen binding to stimulated platelets, we have examined the effects of synthetic protease inhibitors on both fibronectin binding to thrombin-stimulated platetets and fibronectin-mediated cell attachment.
To exclude the direct inhibitory effect of the agents against thrombin, paraformaldehyde-fixed thrombin-stimulated platelets which expressed fibronectin-binding sites were used in this study. Among the synthetic inhibitors examined, FUT-175 and FUT-5923 which have amidinonaptol in their structure as active inhibitory sites, blocked the binding of 125I-fibronectin to thrombin-stimulated platelets dose-dependently. 125I-fibrinogen binding to ADP-stimulated fixed platelets was also inhibited by both FUT-175 and FUT-5923. These data indicated that the inhibition of amidinonaphtol derivatives was not via blockade of binding site expression.
Attachment of normal rat kidney fibroblasts to fibronectin-coated plate was inhibited by these amidinonaphtol derivatives, dose dependently. The agents were also affected fibronectin dependent cellular spreading.
These results suggest that the inhibitory effects of amidinonaphtol derivatives on the cellular interaction with these adhesive proteins might be related to conformational characteristics, not to their inhibitory activities against proteases.