title: Expression of inducible nitric oxide synthase in mice: pharmacological evaluation of adenosine receptor agonists.
abstract: Inhibition of inducible nitric oxide (NO) synthase during endotoxaemia may be of therapeutic value. We have previously shown that pretreatment of mice with adenosine receptor agonists 1 h before lipopolysaccharide administration results in a dose-dependent reduction of plasma nitrite and nitrate (NOx-) levels. This report examines the effects of adenosine receptor agonists, 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA), R-phenylisopropyl-adenosine (R-PIA) and 5'-(N-cyclopropyl)carboxamidoadenosine (CPCA), on the level of inducible NO synthase expression in a model of liver inflammation induced by lipopolysaccharide. Following lipopolysaccharide administration (10 mg/kg, i.p.), liver mRNA expression peaked at 3 h and declined to 35% of maximal level after 24 h. Pretreatment with adenosine receptor agonists (0.001 mg/kg to 5 mg/kg, i.p.) depressed inducible NO synthase mRNA expression significantly. Down-regulation of inducible NO synthase mRNA expression corresponded with changes in plasma NOx- level as well as activity of NO synthase in the liver. Administration of R-PIA (5 mg/kg, i.p.) increased the survival of animals injected with a lethal dose of lipopolysaccharide. Thus adenosine receptor agonists may useful as anti-inflammatory agents in the treatment of endotoxaemia.
authors.affiliation: Department of Surgery, National University of Singapore, Singapore.
authors.forename: S M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: W M
authors.initials: WM
authors.lastname: Hon
authors.forename: V J
authors.initials: VJ
authors.lastname: Chhatwal
authors.forename: H E
authors.initials: HE
authors.lastname: Khoo
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D019001:Nitric Oxide Synthase; D000241:Adenosine