TISSUE- AND DOSE-DEPENDENT ALTERATION OF STRESS-INDUCIBLE PROTEINS BY β_2-ADRENOCEPTOR AGONIST, SALBUTAMOL, IN RATS

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概要

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• The effects of selective β_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 β_2-adrenoceptor agonist, on the induction of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α 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-1β and TNF-α 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 cardiomyo-cytes 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-depen-dently alters the expression of stress-inducible proteins.

• 日本トキシコロジー学会の論文
• 2005-12-21

著者

• YOSHIDA Takemi

  Department of Biochemical Toxicology, School of Pharmacy, Showa University

• Tanaka Satoru

  Division of Toxicology, National Institute of Health Sciences

• TANAKA Satoru

  Toxicology Laboratory, Kissei Pharmaceutical Co., Ltd.

• TSUTSUI Masaru

  Toxicology Laboratory, Kissei Pharmaceutical Co., Ltd.

• KISHIDA Tomoyuki

  Toxicology Laboratory, Kissei Pharmaceutical Co., Ltd.

• Yoshida Tomoko

  Department Of Nuclear Engineering Nagoya University

• Yoshida Takemi

  Dept.biochem.toxicol. Showa Univ.

• Yoshida T

  Department Of Biochemical Toxicology School Of Pharmaceutical Science Showa University

• Yoshida Takemi

  Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University

• Yoshida T

  Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University

• Tsutsui Masaru

  Toxicology Laboratory Kissei Pharmaceutical Co. Ltd.

• Tsutsui Masaru

  Division Of Laboratory Animal Research Research Center For Human And Environmental Sciences Shinshu

• Tanaka Satoru

  Division Of Pharmacology National Institute Of Hygienic Sciences

• Murakami Makoto

  Toxicology Research Laboratory R & D Kissei Pharmaceutical Co. Ltd.

• Yoshida Takemi

  Department Of Biochemical Toxicology School Of Pharmaceutical Science Showa University

• Yoshida Teiji

  Department Of Physics Faculty Of Science Tohoku University

• Kuroda Junji

  Toxicology Lab. Kissei Pharmaceutical Co. Ltd.

• Kuroda J

  Toxicology Research Laboratory R&d Kissei Pharmaceutical Co. Ltd.

• Kuroda Junji

  Toxicology

• YAMAGISHI Ryoichi

  Division of Toxicological Research, Kissei Pharmaceutical Co. Ltd.

• KISHIDA Tomoyuki

  Division of Toxicological Research, Kissei Pharmaceutical Co. Ltd.

• MURAKAMI Makoto

  Division of Toxicological Research, Kissei Pharmaceutical Co. Ltd.

• KURODA Junji

  Division of Toxicological Research, Kissei Pharmaceutical Co. Ltd.

• Yoshida Takahiko

  Department Of Environmental Health Division Of Community And Environmental Health Tokai University S

• Kishida Tomoyuki

  Toxicology Laboratory Kissei Pharmaceutical Co. Ltd.

• Tanaka S

  Toxicology Laboratory Kissei Pharmaceutical Co. Ltd.

• Yoshida Takemi

  School Of Pharmaceutical Sciences Showa University

• Tanaka Satoru

  Division Of Internal Medicine Shizuoka City Hospital

• Yamagishi Ryoichi

  Division Of Toxicological Research Kissei Pharmaceutical Co. Ltd.

• Yoshida Takemi

  Pfizer Japan Inc. Drug Safety R&d Pfizer Global R&d

• Tanaka Satoru

  Division Of Internal Medicine And Thoracic Surgery Shizuoka City Hospital

• Takayama Satoshi

  Research Department Saitama Daiichi Pharmaceutical Co. Ltd. Japanese Pharmaceutical Manufacturers Association

• Yoshida Tomoko

  Department of Biochemical Toxicology, School of Pharmacy Showa University

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