Inhibition of PAF-induced activation of human platelets by verapamil.

Verapamil, an inhibitor of calcium channels, was shown to inhibit PAF-induced platelet activation. In the presence of 50 microM Verapamil both thromboxane (Tx) formation and release of ATP from dense granules induced by 100 nM PAF was completely inhibited. This concentration of Verapamil only produced partial inhibition of PAF-induced aggregation. It also reduced the size of the PAF-induced calcium (Ca2+) transient demonstrated in Fura-2 loaded platelets. In the absence of extracellular Ca2+, following chelation by EGTA, PAF was still able to induce a Ca2+ transient confirming the requirement of both intra and extracellular Ca2+ for PAF-induced platelet activation. 100 microM Verapamil was able to completely abolish the calcium transient induced by low doses of PAF. These results further suggest that Verapamil is able to inhibit PAF-induced platelet activation by mechanisms apart from blocking Ca2+ channels.