Effect of cetiedil on the superoxide-generating system of porcine neutrophils.
Cetiedil, alpha-cyclohexyl-3-thiopheneacetic acid 2-(hexahydro-1H-azepin-1-yl)-ethyl ester, was found to inhibit the generation of superoxide (O2-) by porcine neutrophils exposed to various stimulators. The concentration of cetiedil required for 50% inhibition was about 45 microM when neutrophils were stimulated by phorbol myristate acetate. Cetiedil not only decreased the rate of generation of O2-, but prolonged the lag time prior to the production of O2-. The inhibitory effect of cetiedil on the O2(-)-generating activity of the NADPH oxidase in the membrane vesicles was less than that on whole cells; the concentration of cetiedil necessary for 50% inhibition was about 250 microM. To study the mechanism of cetiedil's effect on the membrane, the transmembrane potential of neutrophils and the intracellular free Ca2+ concentration were monitored by using fluorescence probes, diS-C3-(5), and quin-2, respectively. Cetiedil caused depolarization of the membrane potential and increased the intracellular free Ca2+. These results indicate that integrity of ionic distribution is necessary to activate the O2(-)-generating system of neutrophils.
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003574:Cytochrome c Group / Q000097:blood; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000097:blood*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001381:Azepines; D003574:Cytochrome c Group; D014665:Vasodilator Agents; D003208:Concanavalin A; D013481:Superoxides; C006955:cetiedil; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide