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.
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000302:isolation & purification; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D010972:Platelet Activating Factor; D013449:Sulfonamides; D014268:Trifluoperazine; D000001:Calcimycin; C017967:W 7; D002118:Calcium