Expression of inducible nitric oxide synthase in mice: Pharmacological evaluation of adenosine receptor agonists

• Published in: European journal of pharmacology Vol. 316; no. 2; pp. 287 - 296
• Main Authors: Moochhala, Shabbir M., Hon, Wei-Min, Chhatwal, Vikram J.S., Khoo, Hoon-Eng
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05-12-1996; Elsevier
• Subjects: Adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide); Animals; Anti-inflammatory; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Dose-Response Relationship, Drug; Lipopolysaccharides - pharmacology; Liver - drug effects; Male; Medical sciences; Mice; Mice, Inbred Strains; mRNA expression; Nitric oxide (NO); Nitric oxide (NO) synthase; Nitric Oxide Synthase - metabolism; Pharmacology. Drug treatments; Polymerase Chain Reaction; Vasodilator Agents - pharmacology; Adenosine; Nitric oxide (NO) synthase; Anti-inflammatory; Nitric oxide (NO); mRNA expression; Agonist; Enzyme; Liver; Rodentia; Antiinflammatory agent; Hepatic disease; Inflammation; In vitro; Nitric-oxide synthase; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Enzymatic activity; Mouse; Animal; Oxidoreductases; Adenosine receptor; Endotoxemia
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(96)00677-2

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 (NO
−
x
) levels. This report examines the effects of adenosine receptor agonists. 5′-
N-ethylcarboxamidoadenosine (NECA),
N
6-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 NO
−
x
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.