Calmodulin antagonists inhibit aggregation of human, guniea pig and rabbit platelets induced with platelet activating...

Three calmodulin (CM) antagonists W-7, W-5 and trifluoperazine (TFP) were tested for ability to prevent aggregation of human, guinea pig, and rabbit platelets induced by 7.88 microM PAF. The naphthalene sulfonamide derivatives, W-7 and W-5, were active in all species, W-5 being 1,5--5.7-times less potent than W-7, in accordance with W-5 being a weaker CM inhibitor. ED50-Values for TFP were 155, 160 and 255 microM for rabbit, human and guinea pig platelets, respectively. Results are consistent with the notion that some substances antagonizing CM may inhibit PAF aggregation effects. W-7 is most effective on human platelets (ED50 51.5 microM). High concentrations of TFP required to antagonize PAF-induced aggregation cautions against ascribing its effects solely to an inhibitory effect on CM.