2000 Fiscal Year Final Research Report Summary
Quantitative and Molecular Mechanism-Based Analysis of Factors Interfering with Macromolecular Drug Targeting
| Project/Area Number |
11672150
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
HAYASHI Yayoi Nagoya City University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 講師 (00117847)
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| Co-Investigator(Kenkyū-buntansha) |
YUASA Hiroaki Nagoya City University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20191471)
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| Project Period (FY) |
1999 – 2000
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| Keywords | macromolecular drug / fractionated heparin / targeting / scavenger receptor / liver parenchymal cell / Kupffer cell / peritoneal macrophage / brain capillary endothelial cell |
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| Research Abstract |
It was found, in each of the Kupffer cell and the liver parenchymal cell of the rat, that scavenger receptors involved in the uptake of fractionated heparin can be classified into two types, in terms of sensitivity to maleylated bovine serum albumin (Mal-BSA). Although those in the Kupffer cell were sensitive to acetylated low density lipoprotein (Ac-LDL), those in the liver parenchymal cell were not The Mal-BSA sensitive one in the Kupffer cell may belong to class A scavenger receptors, while the others do not seem to belong any type of scavenger receptor documented in the literature. More detailed investigation should be required about multiplicity and tissue and cellular distributions of scavenger receptors, including those found in the peritoneal macrophage and the brain capillary endothelial cell, to devise strategies for regulating scavenger receptor-mediated disposition of fractionated heparin and some other anionic macromolecular drugs.
We are currently working on cloning of class A scavenger receptors from the rat Kupffer cell, based on cDNA information of those in the human, rabbit and rat. Cloned receptors should be useful for further investigating into the uptake mechanism. Also under investigation is quantitative in vitro-in vivo correlation of the effect of Mal-BSA on fractionated heparin uptake by the liver, which was more profound in vivo.
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Research Products
(8 results)
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[Publications] Watanabe, J., Haba, M., Tanaka, C., Inoue, K., Nakmura, T.and Yuasa, H.: "Scavenger receptor-mediated uptake of fractionated [^3H] heparin in rat peritoneal macrophages."Xenobio.Metabol.Dispos.. 15-1. 1-7 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hoshino, M., Hirashima, N., Inoue, K., Yuasa, H., Nakanishi, M.and Watanabe, J.: "Cloning and functional analysis of scavenger receptors involved in the uptake of fractionated heparin."Xenobio.Metabol.Dispos.. 15-S. 203 (2000)
Description
「研究成果報告書概要(欧文)」より
