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Inactivation of nitric oxide synthases and cellular nitric oxide formation by N6-iminoethyl-L-lysine and N5-iminoethyl-L-ornithine.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1998 Jun 05; Vol. 350 (2-3), pp. 325-34. - Publication Year :
- 1998
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Abstract
- The kinetics of inactivation of affinity-purified nitric oxide synthase isoforms by N6-iminoethyl-L-lysine (NIL) and N5-iminoethyl-L-ornithine (NIO) has been examined. Each of the agents produced a time and concentration dependent first order inactivation of the nitric oxide synthase isoforms that required exposure of the NO synthase to drug under conditions that supported catalysis, consistent with the proposal that these agents act as alternate substrate, mechanism-based inactivators. As measured at 100 microM arginine, NIL and NIO were equally efficient as inactivators of the cytokine-inducible nitric oxide synthase exhibiting apparent second order inactivation rate constants of 31.5 and 32.0 mM(-1) min(-1) respectively. By contrast, NIL and NIO were less efficient as inactivators of the constitutive neuronal nitric oxide synthase isoform exhibiting apparent second order inactivation rate constants of 0.79 and 8.4 mM(-1) min(-1) respectively. As measured at 100 microM extracellular arginine, NIL and NIO produced a time and concentration dependent inactivation of the NO synthetic capability of cytokine-induced murine macrophage RAW 264.7 cells exhibiting apparent second order inactivation rate constants of 3.1 and 1.8 mM(-1) min(-1). The inactivated RAW cell NO synthetic capability was restored to 30% of its pretreatment value over a 3-h period despite the presence of cycloheximide.
- Subjects :
- Animals
Cytokines pharmacology
Guanidines pharmacology
Isoenzymes antagonists & inhibitors
Isoenzymes metabolism
Kinetics
Lysine pharmacology
Methemoglobin metabolism
Mice
Ornithine pharmacology
Oxyhemoglobins metabolism
Enzyme Inhibitors pharmacology
Lysine analogs & derivatives
Nitric Oxide biosynthesis
Nitric Oxide Synthase antagonists & inhibitors
Ornithine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 350
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 9696424
- Full Text :
- https://doi.org/10.1016/s0014-2999(98)00267-2