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 bloc...

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Bibliographic Details
Published in:Prostaglandins & other lipid mediators 1998-05, Vol.56 (1), p.1-6
Main Authors: Hartfield, Perry J, Robinson, John M
Format: Article
Language:English
Subjects:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology
Animals
Arachidonic acid
Arachidonic Acid - metabolism
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
calmodulin
Calmodulin - antagonists & inhibitors
Calmodulin - metabolism
Enzyme Activation
Enzyme Inhibitors - pharmacology
Guinea Pigs
NADPH
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
neutrophils
Neutrophils - enzymology
Nitric Oxide Synthase - antagonists & inhibitors
Onium Compounds - pharmacology
Spectrophotometry
Staurosporine - pharmacology
Sulfonamides - pharmacology
superoxide
Superoxides - metabolism
Vasodilator Agents - pharmacology
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Summary: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.
ISSN:1098-8823
DOI:10.1016/S0090-6980(98)00036-7