Arachidonic acid activates NADPH oxidase by a direct, calmodulin-regulated mechanism.
In intact neutrophils, arachidonic acid rapidly and transiently activated NADPH oxidase-mediated superoxide generation. Inhibitors of protein kinases (staurosporine and H-7) failed to markedly attenuate arachidonic acid-stimulated superoxide generation. Conversely, the calmodulin antagonist W-7 blocked this arachidonic acid-stimulated response. Similarly, diphenylene iodonium potently inhibited superoxide release. These results suggest that arachidonic acid directly activates the membrane-associated NADPH oxidase and calmodulin and/or calmodulin-binding proteins are required for the assembly of the active oxidase.
Department of Cell Biology, Neurobiology and Anatomy, Ohio State University, Columbus 43210, USA. P.Hartfield@flinders.edu.au
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Robinson
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009861:Onium Compounds / Q000494:pharmacology; D013053:Spectrophotometry; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D002147:Calmodulin; D004791:Enzyme Inhibitors; D009861:Onium Compounds; D013449:Sulfonamides; D014665:Vasodilator Agents; D013481:Superoxides; D016718:Arachidonic Acid; C017967:W 7; C007517:diphenyleneiodonium; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019311:Staurosporine