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.

Original languageEnglish (US)
Pages (from-to)571-576
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume253
Issue number3
DOIs
StatePublished - Dec 30 1998

Fingerprint

Nitric Oxide Synthase
Nitric Oxide
Arginine
Pleurobranchaea
Molluscs
Tissue
Spin Trapping
omega-N-Methylarginine
Nerve Tissue
Aplysia
Gastropoda
Mollusca
Dithiothreitol
Poisons
NG-Nitroarginine Methyl Ester
Electron Spin Resonance Spectroscopy
NADP
Glutathione
Cysteine
Paramagnetic resonance

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Non-enzymatic production of nitric oxide (NO) from NO synthase inhibitors. / Moroz, Leonid L.; Norby, Shong Wan; Cruz, Lou Ann; Sweedler, Jonathan V; Gillette, Rhanor; Clarkson, Robert B.

In: Biochemical and Biophysical Research Communications, Vol. 253, No. 3, 30.12.1998, p. 571-576.

Research output: Contribution to journalArticle

Moroz, Leonid L. ; Norby, Shong Wan ; Cruz, Lou Ann ; Sweedler, Jonathan V ; Gillette, Rhanor ; Clarkson, Robert B. / Non-enzymatic production of nitric oxide (NO) from NO synthase inhibitors. In: Biochemical and Biophysical Research Communications. 1998 ; Vol. 253, No. 3. pp. 571-576.
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AU - Clarkson, Robert B.

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