Metabolism of the Intravenously Administered Recombinant Human Basic Fibroblast Growth Factor, Trafermin, in Liver and Kidney : Degradation Implicated in Its Selective Localization to the Fenestrated Type Microvasculatures
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概要
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The fate of trafermin (recombinant human basic fibroblast growth factor) was examined after intravenous administration of its iodinated form to rats. Autoradiography at 5 and 30 min after the injection showed that ^<125>I-trafermin is localized specifically in the fenestrated endothelium through binding to heparan sulfate proteoglycans (HSPG) in liver, kidney, adrenal, spleen, hypophysis and bone marrow. Metabolites in the organs were examined at 5 min and 24 h after the injection. More than 73% of radioactivity in liver and kidney was extractable at either time point, and a large majority of the extracted radioactivity was heparin-binding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the substantial radioactivity recovered from liver and kidney can commonly be attributed to a peptide with the same molecular weight as the intact trafermin (B-1,17.7 kDa) and only three truncated metabolites (B-2,15.0 kDa; B-3,7.2 kDa; B-4,4.2 kDa). Because no truncated metabolites were found in serum, these metabolites seem to be produced inherently in liver and kidney. Although they all retained heparin-binding capacity, only B-1 and B-2 exhibited a stimulatory effect on proliferation of endothelial cells, and these bioactive peptides disappeared completely from liver within a day, indicating a rapid inactivation process in the organs. Taken together with the morphological evidence on autoradiography, it seems most likely that the injected trafermin could be inactivated in sinusoidal endothelial cells, probably through a well-known internalization mechanism of the basic fibroblast growth factor-HSPG complex.
- 公益社団法人日本薬学会の論文
- 1997-07-15
著者
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KIMURA Ryohei
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka
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Kimura Ryohei
Department Of Biopharmacy School Of Pharmaceutical Sciences University Of Shizuoka
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Kimura Ryohei
Department Of Biophamacy School Of Pharmaceutical Sciences University Of Shizuoka
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Furukawa A
Advanced Technology R&d Center Mitsubishi Electric Corporation
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YUGE Takuro
FGF Product Team, Kaken Pharmaceutical Co., Ltd.,
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FURUKAWA Akihiko
Development Research Laboratories, Kaken Pharmaceutical Co., Ltd.,
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NAKAMURA Katsuhiro
Development Research Laboratories, Kaken Pharmaceutical Co., Ltd.,
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NAGASHIMA Yutaka
Development Research Laboratories, Kaken Pharmaceutical Co., Ltd.,
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SHINOZAKI Kohki
Development Research Laboratories, Kaken Pharmaceutical Co., Ltd.,
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NAKAMURA Toshiyuki
Development Research Laboratories, Kaken Pharmaceutical Co., Ltd.,
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Nakamura Katsuhiro
Development Research Laboratories Kaken Pharmaceutical Co. Ltd.
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Yuge Takuro
Fgf Product Team Kaken Pharmaceutical Co. Ltd.
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Shinozaki Kohki
Development Research Laboratories Kaken Pharmaceutical Co. Ltd.
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Nagashima Y
Development Research Laboratories Kaken Pharmaceutical Co. Ltd.
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Nakamura Toshiyuki
Development Research Laboratories Kaken Pharmaceutical Co. Ltd.
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- Metabolism of the Intravenously Administered Recombinant Human Basic Fibroblast Growth Factor, Trafermin, in Liver and Kidney : Degradation Implicated in Its Selective Localization to the Fenestrated Type Microvasculatures
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