Selective inhibition of the inducible nitric oxide synthase by aminoguanidine

Thomas P. Misko, William M. Moore, Thomas P. Kasten, G. Allen Nickols, John A. Corbett, Ronald Tilton, Michael L. McDaniel, Joseph R. Williamson, Mark G. Currie

Research output: Contribution to journalArticle

690 Citations (Scopus)

Abstract

Overproduction of the free radical nitric oxide (NO) has been implicated in the pathogenesis of a variety of inflammatory and immunologically mediated diseases as well as complications of diabetes. In the present study we have demonstrated that aminoguanidine selectively inhibits the cytokine-inducible isoform of NO synthase which appears to be responsible for the excess production of NO linked to these disease states. By using organ, cell and enzyme-based measurements we have shown that aminoguanidine is equipotent to NG-monomethyl-L-arginine (L-NMA) as an inhibitor of the cytokine-induced isoform of NO synthase but is 10 to 100-fold less potent as an inhibitor of the constitutive isoform. Thus, aminoguanidine may be useful as a selective inhibitor of the inducible NO synthase in the treatment of disease states characterized by the pathological overproduction of NO.

Original languageEnglish (US)
Pages (from-to)119-125
Number of pages7
JournalEuropean Journal of Pharmacology
Volume233
Issue number1
DOIs
StatePublished - Mar 16 1993
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Nitric Oxide
Protein Isoforms
Cytokines
omega-N-Methylarginine
Diabetes Complications
Nitric Oxide Synthase
Free Radicals
Enzymes
pimagedine

Keywords

  • Aminoguanidine
  • Nitric oxide synthase
  • Selective inhibitor inducible

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Misko, T. P., Moore, W. M., Kasten, T. P., Nickols, G. A., Corbett, J. A., Tilton, R., ... Currie, M. G. (1993). Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. European Journal of Pharmacology, 233(1), 119-125. https://doi.org/10.1016/0014-2999(93)90357-N

Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. / Misko, Thomas P.; Moore, William M.; Kasten, Thomas P.; Nickols, G. Allen; Corbett, John A.; Tilton, Ronald; McDaniel, Michael L.; Williamson, Joseph R.; Currie, Mark G.

In: European Journal of Pharmacology, Vol. 233, No. 1, 16.03.1993, p. 119-125.

Research output: Contribution to journalArticle

Misko, TP, Moore, WM, Kasten, TP, Nickols, GA, Corbett, JA, Tilton, R, McDaniel, ML, Williamson, JR & Currie, MG 1993, 'Selective inhibition of the inducible nitric oxide synthase by aminoguanidine', European Journal of Pharmacology, vol. 233, no. 1, pp. 119-125. https://doi.org/10.1016/0014-2999(93)90357-N
Misko TP, Moore WM, Kasten TP, Nickols GA, Corbett JA, Tilton R et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. European Journal of Pharmacology. 1993 Mar 16;233(1):119-125. https://doi.org/10.1016/0014-2999(93)90357-N
Misko, Thomas P. ; Moore, William M. ; Kasten, Thomas P. ; Nickols, G. Allen ; Corbett, John A. ; Tilton, Ronald ; McDaniel, Michael L. ; Williamson, Joseph R. ; Currie, Mark G. / Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. In: European Journal of Pharmacology. 1993 ; Vol. 233, No. 1. pp. 119-125.
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