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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.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Moochhala SM,Hon WM,Chhatwal VJ,Khoo HE

doi

10.1016/s0014-2999(96)00677-2

subject

Has Abstract

pub_date

1996-12-05 00:00:00

pages

287-96

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(96)00677-2

journal_volume

316

pub_type

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