Abstract
Effects of calcium-channel blockers on platelet activation were examined in vitro by using diltiazem and verapamil. They showed inhibitory effects on aggregation, ATP- and platelet factor 4(PF-4)-release reaction and thromboxane A2 generation by collagen. An inhibition of thromboxane A2 generation, measured as thromboxane B2 (TXB2), was dose-dependent and more sensitive than other parameters examined. Diltiazem was more potent than verapamil in the inhibition of PF-4 release and (TXB2) generation.
Addition of chelating extracellular calcium by EDTA did not cause ADP- or collagen-induced platelet aggregation, but thrombin-induced aggregation was still remained. In this condition, effects of Ca-channel blockers were greatly reduced. Thrombin-induced phosphorylations of 20Kd and 40Kd proteins were not inhibited by them in EDTA-containing medium, either. These results suggest an importance of extracellular calcium on the mechanism of effects produced by Ca-channel blockers.
