دورية
Non-Enzymatic Production of Nitric Oxide (NO) from NO Synthase Inhibitors
| العنوان: | Non-Enzymatic Production of Nitric Oxide (NO) from NO Synthase Inhibitors |
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| المؤلفون: | Moroz, Leonid L., Norby, Shong Wan, Cruz, LouAnn, Sweedler, Jonathan V., Gillette, Rhanor, Clarkson, Robert B. |
| المصدر: | Biochemical and Biophysical Research Communications; December 1998, Vol. 253 Issue: 3 p571-576, 6p |
| مستخلص: | The gaseous signal molecule, nitric oxide (NO•), is generated enzymatically by NO synthase (NOS) from L-arginine. Overproduction of NO contributes to cell and tissue damage assequelaeof infection and stroke. Strategies to suppress NO synthesis rely heavily on guanidino-substituted L-arginine analogs (L-NAME, L-NA, L-NMMA, L-NIO) as competitive inhibitors of NOS, which are often used in high doses to compete with millimolar concentrations of intracellular arginine. We show that these analogs are also a source for non-enzymatically produced NO. Enzyme-independent NO release occurs in the presence of NADPH, glutathione, L-cysteine, dithiothreitol and ascorbate. This non-enzymatic synthesis of NO can produce potentially toxic, micromolar concentrations of NO and can oppose the effects of NOS inhibition. NO production driven by NOS inhibitors was demonstratedex vivoin the central nervous and peripheral tissues of gastropod molluscsAplysiaandPleurobranchaeausing electron paramagnetic resonance and spin-trapping techniques. These results have important implications for therapeutic regulation of NO homeostasis. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 0006291X 10902104 |
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| DOI: | 10.1006/bbrc.1998.9810 |