Calmodulin antagonists inhibit formation of platelet-activating factor in stimulated human neutrophils

Human polymorphonuclear leukocytes in the presence of the Ca2+ ionophore A23187 plus Ca2+ incorporated exogenously-added [3H]acetate or 1-0-[3H]-alkyl-sn-glycero-3-phosphocholine (lysoplatelet-activating factor) into platelet-activating factor (PAF,1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine). The incorporation of these radiolabels into PAF by stimulated neutrophils was inhibited by the calmodulin antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide. These two drugs were active at concentrations similar to their respective binding constants to purified calmodulin, suggesting a possible involvement of calcium-activated calmodulin in PAF biosynthesis.