Inhibition of cytokine-induced inducible nitric oxide synthase expression by glucagon and cAMP in cultured hepatocytes

Smith, F S, Ceppi, E D and Titheradge, M A (1997) Inhibition of cytokine-induced inducible nitric oxide synthase expression by glucagon and cAMP in cultured hepatocytes. Biochemical Journal, 326 (1). pp. 187-192. ISSN 02646021

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Abstract

Addition of lipopolysaccharide plus interferon ¿, tumour necrosis factor a and interleukin 1ß to cultured hepatocytes resulted in the induction of inducible nitric oxide synthase (iNOS) activity as measured by NO3- + NO2- formation, the conversion of L-[U-14C]arginine into citrulline and Western blotting of the iNOS protein. The inclusion of 1 µM glucagon during the induction period significantly decreased the effect of the cytokines on iNOS activity, the major effect being at the level of the total amount of protein, rather than alterations in substrate supply or covalent modification of the existing protein. In contrast, 1 µM insulin was without effect. The effect of glucagon was mediated via cAMP and could be mimicked by the presence of either dibutyryl cAMP or forskolin to activate adenylate cyclase directly. It was rapid in onset and long-lived, a 30 min pre-treatment period protecting the cells from the induction of NO synthesis over the next 21 h in the presence of cytokines. Addition of glucagon at any time point up to 9 h after treatment of the cells with lipopolysaccharide plus the cytokines resulted in a significant inhibition of iNOS activity, glucagon being most potent when added during the first 3 h.

Item Type: Article
Additional Information: This was the first evidence that glucagon acting via cAMP could inhibit the induction of nitric oxide synthase in the liver
Schools and Departments: School of Life Sciences > Biochemistry
Brighton and Sussex Medical School > Division of Medical Education
Depositing User: Michael Titheradge
Date Deposited: 06 Feb 2012 18:26
Last Modified: 22 Sep 2017 13:13
URI: http://sro.sussex.ac.uk/id/eprint/16309
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