Studies on the mechanism of superoxide release from human neutrophils stimulated with arachidonate.
cis-Unsaturated fatty acids stimulate release of superoxide (O-2) by human neutrophils (Badwey, J. A., Curnutte, J. T., Robinson, J. M., Berde, C. B., Karnovsky, M. J., and Karnovsky, M. L. (1984) J. Biol. Chem. 259, 7870-7877). The rate of O-2 release due to arachidonate (105 +/- 24 S.D., nmol of O-2/min/10(7) cells) was comparable to optimal values obtained with other stimuli. Antagonists of calcium-binding proteins (i.e. phenothiazines, naphthalene sulfonamides) inhibited the release of O-2 in a fashion compatible with the involvement of calmodulin in these phenomena. Synthetic substrates for and an inhibitor of chymotrypsin-like proteases (e.g. N-benzoyl-L-tyrosine ethyl ester, L-1-tosylamido-2-phenylethyl chloromethyl ketone) also blocked O-2 release. Antagonists of calcium-binding proteins and of proteases were effective in this context with neutrophils stimulated with a variety of agents. The implications of these data for recent reports concerning the mechanism of action of cis-unsaturated fatty acids on phagocytes is discussed.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013481:Superoxides / Q000097:blood*; D014268:Trifluoperazine / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D001095:Arachidonic Acids; D008041:Linoleic Acids; D011480:Protease Inhibitors; D013449:Sulfonamides; D013481:Superoxides; D014268:Trifluoperazine; D016718:Arachidonic Acid; C006716:benzoyltyrosine ethyl ester; D014443:Tyrosine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D019787:Linoleic Acid