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Biochem Biophys Res Commun. 1998 Dec 30;253(3):571-6.

Non-enzymatic production of nitric oxide (NO) from NO synthase inhibitors.

Author information

1
Department of Neuroscience, The Whitney Laboratory, University of Florida, St. Augustine 32086-8623, USA. moroz@whitney.ufl.edu

Abstract

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 as sequelae of 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 demonstrated ex vivo in the central nervous and peripheral tissues of gastropod molluscs Aplysia and Pleurobranchaea using electron paramagnetic resonance and spin-trapping techniques. These results have important implications for therapeutic regulation of NO homeostasis.

PMID:
9918769
DOI:
10.1006/bbrc.1998.9810
[Indexed for MEDLINE]

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