Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs 1

  title={Inhibition of macrophage and endothelial cell nitric oxide synthase by diphenyleneiodonium and its analogs 1},
  author={Dennis J. Stuehr and O A Fasehun and Nyoun Soo Kwon and Steven. S. Gross and Jos{\'e} Antonio Gonz{\'a}lez and Roberto Levi and Carl F. Nathan},
  journal={The FASEB Journal},
  pages={103 - 98}
The cofactor requirements of macrophage nitric oxide (NO·) synthase suggest involvement of an NADPH‐dependent flavoprotein. This prompted us to test the effect of the flavoprotein inhibitors diphenyleneiodonium (DPI), di‐2‐thienyliodonium (DTI), and iodoniumdiphenyl (ID) on the NO· synthases of macrophages and endothelium. DPI, DTI, and ID completely inhibited NO· synthesis by mouse macrophages, their lysates, and partially purified macrophage NO· synthase. Inhibition of NO· synthase by these… 

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The findings suggest that activated macrophages release large amounts of neurotoxic molecules and that norharmane may represent a prototype compound to study macrophage involvement in inflammatory brain damage.

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The known and proposed mechanisms of the regulation of iNOS induction, and on agents that can modulate NO release once the active enzyme has been expressed in the macrophage are focused on.

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Regulation of the L-arginine-dependent and tetrahydrobiopterin-dependent biosynthesis of nitric oxide in murine macrophages.

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The inhibition by diphenyleneiodonium and its analogues of superoxide generation by macrophages.

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Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide

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A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of

EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages.

  • J. LancasterJ. Hibbs
  • Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
Results show that loss ofIron-containing enzyme function in CAM is a result of the formation of iron-nitrosyl complexes induced by the synthesis of nitric oxide from the oxidation of a terminal guanidino nitrogen atom of L-arginine.

Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite.

An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is shown to cause this pattern of metabolic inhibition in cytotoxic activated macrophages.

The effect of the inhibitor diphenylene iodonium on the superoxide-generating system of neutrophils. Specific labelling of a component polypeptide of the oxidase.

NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content. Addition of