Inhibitory Effect of Nifedipine on Tumor Necrosis Factor α-Induced Neovascularization in Cultured Choroidal Explants of Streptozotocin-Diabetic Rat(Pharmacology)

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概要

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• We have previously reported that the N^ε-(carboxymethyl)lysine (CML) adduct, a major structure of an advanced glycation end product, facilitates proliferation of CD34^+ endothelial progenitor cells budded from cultured choroidal explants and produces immature vessel-like structures in fibrin gel. The CML adduct is accumulated and facilitates immature neovascularization in cultured choroidal explants of streptozotocin (STZ)-induced diabetic rat. The CML-enhanced neovascularization activity is associated with the actions of tumor necrosis factor (TNF) α, vascular endothelial growth factor and platelet-derived growth factor released from the choroidal explant (Kobayashi et al., Biol. Pharm. Bull., 27, 1382-1387 (2004) ; 27, 1565-1571 (2004)). The present study was investigated an inhibitory effect of a dihydropyridine calcium antagonist nifedipine on TNF α-induced choroidal neovascularization in the STZ-diabetic rat. TNF α(1-100ng/ml) increased neovascularization of cultured choroidal explants in the age-matched normal rat but did not increase it in the diabetic rat. Anti-TNF α antibody (1 : 1000) decreased the neovascularization in the diabetic rat but not in the normal rat. Nifedipine (1μм) inhibited TNF α-induced neovascularization of the normal choroidal explant in a non-competitive manner. Nifedipine (1μм) also inhibited the diabetic state-induced neovascularization and its inhibitory action was reversed by TNF α (1-10 ng/ml). In conclusion, STZ-diabetic state facilitated choroidal neovascularization through the release of TNF α. Nifedipine inhibited the action of TNF α probably by blocking voltage-dependent Ca^<2+> channels in the endothelial progenitor cells of the diabetic choroid.

• 公益社団法人日本薬学会の論文
• 2005-02-01

著者

• SUZUKI Miho

  Department of Biotechnology, The University of Tokyo

• 木村 郁子

  富山医薬大薬薬品作用学

• 木村 郁子

  富山医科薬科大学

• 木村 郁子

  富山医科薬科大学 臨床薬理学

• 木村 郁子

  富山医科薬科大学大学院薬学研究科臨床薬理学

• 木村 郁子

  富山医科薬科大学 大学院薬学研究科臨床薬理学講座

• KIMURA Ikuko

  Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences, Toyama medical and Pharmaceu

• KOBAYASHI Shinjiro

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• TSUNEKI Hiroshi

  Department of Clinical Pharmacology, Toyama Medical and Pharmaceutical University

• FUKUTA Mizuki

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• Fukuta Mizuki

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Fukuta Mizuki

  北陸大学 薬 薬理

• Inaba Kazuhiko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Inaba Kazuhiko

  北陸大学 薬 薬理

• Suzuki Miho

  Department Of Biotechnology The University Of Tokyo

• Kimura I

  Toyama Medical And Pharmaceutical Univ. Toyama Jpn

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Phrmaceutical Sciemes Toyama Medical And Pharmaceutic

• Kimura I

  Department Of Ophthalmology Keio University School Of Medicine

• 木村 郁子

  富山医科薬科大学 薬学部 薬品作用学

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Kobayashi Shinjiro

  Department Of Chemical Pharmacology Toyama Medical And Pharmaceutical University

• Suzuki Miho

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Tsuneki H

  Department Of Clinical Pharmacology University Of Toyama

• Kobayashi S

  Kyoritsu Coll. Pharmacy

• 木村 郁子

  Department Of Clinical Pharmacology Graduate School Of Pharmaceutical Sciences Toyama Medical And Ph

• Suzuki Masahiko

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Tsuneki Hiroshi

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Tsuneki Hiroshi

  富山医科薬科大学大学院薬学研究科 臨床薬理学講座

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical & Pharmace

• Kobayashi Shinjiro

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University:organizat

• Fujihara Mitsuhiro

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Suzuki Miho

  Department Of Biology Faculty Of Science Nagoya University

• Kimura Ikuko

  Deparment Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University

• 木村 郁子

  Department of Food and Nutrition Science, Toyama College

• 木村 郁子

  富山医科薬科大学大学院薬学研究科 臨床薬理学講座

• TSUNEKI Hiroshi

  Department of Clinical Pharmacology,Graduate School of Pharmaceutical Sciences,Toyama Medical and Pharmaceutical

• Kobayashi Shinjiro

  Department of Applied Chemistry, Faculty of Engineering, Kyushu University

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