3-amino-1,2,4-triazole inhibits macrophage NO synthase.
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.
Buchmüller-Rouiller
Y
Y
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Schneider
P
P
Betz-Corradin
S
S
Smith
J
J
Mauël
J
J
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000640:Amitrole / Q000494:pharmacology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000640:Amitrole