Effects of non-steroidal anti-inflammatory drugs on human neutrophil NADPH oxidase in both whole cell and cell-free systems.
The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the respiratory burst oxidase (NADPH oxidase, EC 1.6.99.6) from human neutrophils in both whole cell and fully soluble (cell-free) systems were investigated. Three NSAIDs, indomethacin, salicylic acid and acetylsalicylic acid (aspirin), were found to inhibit the superoxide generation by human neutrophils exposed to phorbol myristate acetate in a whole cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. Concentrations of these NSAIDs required for 50% inhibition of the oxidase (IC50) were: indomethacin (180 microM in both systems), salicylic acid (1.30 mM in the cell-free system, and more than 3.0 mM in the whole cell system) and acetylsalicylic acid (1.35 mM in the cell-free system, and more than 3.0 mM in the whole cell system). In addition, in the cell-free system, these NSAIDs did not change the Km values for NADPH of the oxidase. These results suggest that these NSAIDs, especially indomethacin, concentration-dependently inhibit the reconstitution of the solubilized membrane-bound enzyme by sodium dodecyl sulfate in the cell-free system.
Umeki
S
S
Department of Medicine, Kawasaki Medical School, Okayama, Japan.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; D020156:Salicylic Acid; D001241:Aspirin; D007213:Indomethacin