Article: article from journal or magazin.
3-amino-1,2,4-triazole inhibits macrophage NO synthase.
Biochemical and Biophysical Research Communications
Murine macrophages activated by interferon-gamma and lipopolysaccharide become leishmanicidal through a process involving L-arginine-derived nitrogen oxidation products. Both nitrite secretion and parasite killing by activated macrophages were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino-1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3-amino-1,2,4-triazole, was without effect. Our results suggest that besides its known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is an inhibitor of NO synthase. The resemblance between the tautomeric form of 3-amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate for NO synthase, might be responsible for the observed inhibition.
Amino Acid Oxidoreductases/antagonists &, inhibitors, Amitrole/pharmacology, Animals, Cytosol/enzymology, Dose-Response Relationship, Drug, Interferon-gamma/pharmacology, Leishmania/drug effects, Lipopolysaccharides/metabolism, Macrophage Activation/drug effects, Macrophage Activation/physiology, Macrophages/drug effects, Macrophages/enzymology, Mice, Mice, Inbred CBA, Nitric Oxide/metabolism, Nitric Oxide Synthase
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