MECHANISM RESPONSIBLE FOR "DOWNREGULATION" DURING SUCCESSIVE β-AGONIST ADMINISTRATION IN RAT HEARTS

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概要

• 論文の詳細を見る

• The role of phospholipase (PLase) on the mechanism of the so called "down regulation", which decreases the number of β-adrenergic receptors (β-AR) of rat cardiac membranes during successive β-agonist administration, was investigated. In vivo study: The rats were divided into 3 groups; (1) the control group, untreated; (2) the isoproterenol (ISP) one day group, ISP (10 mg/kg) was subcutaneously injected once; and (3) the ISP 6 days group, ISP (10 mg/kg) was injected once a day for 6 successive days. Binding assay using [^3H] dihydroalprenolol and analysis of the content and the composition of fatty acids in phospholipids in cardiac membranes were conducted. The endogenous PLase activity in heart homogenate and tissue ATP levels were also determined. In the 6 days group, the equilibrium dissociation constant of β-AR was not affected; however the number of β-AR decreased significantly when compared with the control group. Phospholipid content also decreased in parallel with the decrease in the number of β-AR and the composition of fatty acids was altered. However, in the one day group, there were no significant changes in either the number of -AR or the phospholipid content. The PLase activity of heart homogenate increased significantly, and the tissue ATP levels decreased in both the one day and the 6 days group. In vitro study: Cardiac membranes prepared from intact rats were incubated with 0.03 and 0.1 unit of PLase A_2. PLase A_2 reduced the number of -AR dose-dependently. These results suggested that the degradation of membrane phospholipids caused by persistent activation of endogenous PLase is closely related to the decrease in the number of -AR during successive administration of -agonist.

• 社団法人日本循環器学会の論文
• 1985-12-20

著者

• SUGIYAMA Satoru

  Department of Pharmacology, Aichi Medical University School of Medicine

• Ozawa Takayuki

  Department of Biomedical Chemistry and of Internal Medicine, Faculty of Medicine, University of Nago

• Nagai Shuichiro

  Departments of InternaI Medicine, FacuIty of Medicine, University of Nagoya

• Ozawa Takayuki

  Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• Sugiyama Satoru

  Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• Sugiyama Satoru

  Department Of Biomedical Chemistry

• Nagai Shuichiro

  Departments Of Internal Medicine And Biomedical Chemistry

• Ozawa Takayuki

  Departments Of Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• Ozawa Takayuki

  The Department Of Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• Sugiyama Satoru

  Biomedical Chemistyry Faculty Of Medicine University Of Nagoya

• Sugiyama Satoru

  Departments Of Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• TAKAMURA TADANOBU

  Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya

• Ozawa T

  The Department Of Biomedical Chemistry Faculty Of Medicine University Of Nagoya

• Takamura Tadanobu

  Departments Of Biomedical Chemistry University Of Nagoya

• Sugiyama Satoru

  Faculty Of Medicine University Of Nagoya

• Ozawa Takayuki

  Department Of Biomedical Chemistry

• Ozawa Takayuki

  Departments Of Biomedical Chemistry University Of Nagoya

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