Tissue- and dose-dependent alteration of stress-inducible proteins by beta2-adrenoceptor agonist, salbutamol, in rats
Autor: | Satoru Tanaka, Makoto Murakami, Takemi Yoshida, Junji Kuroda, Tomoyuki Kishida, Masaru Tsutsui, Ryoichi Yamagishi |
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Rok vydání: | 2006 |
Předmět: |
Agonist
Lipopolysaccharides Male medicine.medical_specialty medicine.drug_class Nitric Oxide Synthase Type II Spleen Toxicology Proinflammatory cytokine Propanolamines Rats Sprague-Dawley Adrenergic beta-2 Receptor Antagonists Internal medicine medicine Animals Albuterol RNA Messenger Adrenergic beta-2 Receptor Agonists Lung Heat-Shock Proteins Inflammation biology Dose-Response Relationship Drug Myocardium Interleukin Heart Rats Nitric oxide synthase Dose–response relationship Disease Models Animal Endocrinology medicine.anatomical_structure Liver Heme Oxygenase (Decyclizing) biology.protein Cytokines Tumor necrosis factor alpha |
Zdroj: | The Journal of toxicological sciences. 30(4) |
ISSN: | 0388-1350 |
Popis: | The effects of selective beta(2)-adrenoceptor agonists on proinflammatory cytokines and the expression of stress-inducible proteins have not yet been clarified. We investigated the effect of a higher dose (60 mg/kg intravenously) of salbutamol, a selective beta(2)-adrenoceptor agonist, on the induction of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in plasma and the expression of protein and mRNA of metallothioein-1 (MT-1), heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in heart, lung, liver and spleen in rats. The plasma IL-6 concentration was significantly increased after administration with a maximum increase at 3 hr in a dose-dependent manner, but IL-1beta and TNF-alpha concentrations were not changed. MT-1 mRNA increased in heart, lung and liver, but not in spleen, and MT-1 protein increased in endocardium, fibroblasts of lung and periportal regions in liver. HO-1 mRNA was not changed in lung, decreased at 3 hr in liver and spleen, and increased at 6 hr in liver. Contrary to liver, HO-1 mRNA in the heart increased at 3 hr and decreased at 6 hr. HO-1 protein increased in cardiomyocytes and centrilobular regions in the liver. iNOS mRNA increased in lung, liver and spleen, but decreased in the heart, and iNOS protein increased in alveolar type II cells and hepatocytes, and decreased in necrotic cardiomyocytes. In contrast, a lower dose (6 mg/kg intravenously) of salbutamol suppressed lipopolysaccharide-induced HO-1 and iNOS mRNA. We conclude that salbutamol tissue- and dose-dependently alters the expression of stress-inducible proteins. |
Databáze: | OpenAIRE |
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