Interferon-gamma-inducible murine macrophage nitric oxide synthase: studies on the mechanism of inhibition by imidazole agents
| Autor: | B.J. Gribin, D.J. Wolff |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Lipopolysaccharides
Arginine Biophysics Macrophage Nitric Oxide Synthase Biochemistry Cell Line chemistry.chemical_compound Interferon-gamma Mice Structure-Activity Relationship medicine Imidazole Animals Molecular Biology biology Clotrimazole Cytochrome c Macrophages Imidazoles Nitric oxide synthase Kinetics chemistry Enzyme Induction biology.protein Ketoconazole Amino Acid Oxidoreductases Miconazole Nitric Oxide Synthase medicine.drug |
| Zdroj: | Archives of biochemistry and biophysics. 311(2) |
| ISSN: | 0003-9861 |
| Popis: | Citrulline formation by the interferon-γ/lipopolysaccharide-inducible murine macrophage nitric oxide synthase is inhibited reversibly by imidazole, 1-phenylimidazole, 4-phenylimidazole, and 2-phenylimidazole with IC 50 values of 40 μM, 6 μM, 225 μM and >1 mM, respectively. 1-Phenylimidazole inhibited the maximal velocity of citrulline formation but did not alter the concentration of arginine providing half-maximal activity. 1-Phenylimidazole inhibited citrulline formation by the murine macrophage nitric oxide synthase competitively versus (6 R )-5,6,7,8-tetrahydro-L-biopterin (THB) with a K i value of 0.7 μM, but inhibited citrulline formation by Ca 2+ -calmodulin-dependent nitric oxide synthase from GH 3 pituitary cells noncompetitively versus THB with a K i value of 40 μM. Imidazole inhibited citrulline formation by the murine macrophage nitric oxide synthase noncompetitively versus THB with a K i value of 48 μM. Neither imidazole nor 1-phenylimidazoIe inhibited the cytochrome c reductase activity of murine macrophage nitric oxide synthase at concentrations 100-fold higher than their IC 50 values for inhibiting citrulline formation. The antifungal imidazoles miconazole, ketoconazole, and clotrimazole did not inhibit either citrulline formation or cytochrome c reduction by murine macrophage nitric oxide synthase at concentration as high as 200 μM. Ca 2+ -calmodulin-dependent nitric oxide synthase from GH 3 pituitary cells exhibited a K act for THB of 80 nM, while the inducible murine macrophage nitric oxide synthase exhibited a K act of 8 μM. |
| Databáze: | OpenAIRE |
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