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Study on Pharmacokinetics of Bioactive Macromolecular Drug for DDS : Scavenger Receptor-Mediated Internarization and Release of Fractionated [^3H] Heparin

Research Project

Project/Area Number 08672482
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionNagoya City University

Principal Investigator

WATANABE Jun  Nagoya City University, Faculty of Pharmaceutical Sci.Professor, 薬学部, 教授 (80080175)

Co-Investigator(Kenkyū-buntansha) HABA Masami  Nagoya City University, Faculty of Assist.Professor, 薬学部, 助手 (70254307)
YUASA Hiroaki  Nagoya City University, Faculty of Pharmaceutical Sci.Assoc.Professor, 薬学部, 助教授 (20191471)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsfractionated heparin / rat liver parenchymal cells / rat Kupffer cells / peritoneal macrophages / surface binding / intemalization / apparent release constant / scavenger receptor / 肝取り込み / 肝実質細胞 / クッパー細胞 / スカベンジ-受容体 / スカベンジャー様受容体 / エンドサイトーシス / 血漿タンパクとの相互作用
Research Abstract

(1)The concentration-dependent uptake of high molecular weight fractionated heparin (20,000Da) was observed with rat Kupffer cells, liver parenchymal cells in primary culture and peritoneal macrophages. The dissociation constants, K_d for Kupffer cells and peritoneal macrophages were similar to each other showing 5.7 and 6.7 nM,respectively whereas the value for liver parenchymal cells was much lower than those showing 53.5nM.The maximum binding capacity, B_<max> were 1.5 and 1.9 pmol/10^6 cells, respectively for Kupffer cells and peritoneal macrophages, whereas liver parenchymal cells took much larger value of 32.8 pmol/10^6 cells. Thus, the liver parenchymal cells were demonstrated to have larger binding capacity and less affinity to the fractionated heparin comparing to Kupffer cells and peritoneal macrophages..
(2)The dissociation constants, K_d for both Kupffer cells and liver parenchymal cells in primary culture increased with decrease of molecular weight of fractionated heparin, although the maximum binding capacity, B_<max> for both kind of cells remained almost unchanged.
(3)The apparent release constant for intemalized fractionated [^3H] heparin, K_<rel, app> was one-third of the value for the apparent intemalization constant K_<int, app> and decreased when the temperature was lowered from 37゚C to 4゚C.
(4)The apparent release constant for intemalized fractionated [^3H] heparin, K_<rel, app> increased from 0.074 to 0.127h^<-1>, when the intemalized amount of fractionated [^3H] heparin was raised from 0.259 to 5.764 pmol/mg protein. On the other hand, the apparent released constant was not influenced by addition of alpha-globulin, chloroquine or monensin to the incubation medium.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Masami Haba et al.: "Hecromolecule-macromolecule interaction in drug distribution.V.Effects of plasma pnoteins on upteke of fractionated〔3H〕heperin in isolated rat kopffen cells" Biol.Pharm.Bull. 19(10). 1352-1356 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 浦野 公彦 ら: "ラット肝実質細胞における分画heparinの輸送機構:スカベンジャー様レセプターの関与" 薬物動態. 11. S94-S95 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano et al.: "Kinetic characterizetion of binding and in tereatization of frectioneted〔3H〕heparin in rat liver parenchymal cells in primery culture" Biol.Pharm.Bull.20(6). 680-683 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano et al.: "In ternatization of fractionated 〔3H〕 heparin by the scarenger-like recepter in pat liver perenchymal cells in primary culture" Drug Delivery. 4. 181-185 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 巾 正美, 渡辺 淳: "スカベンジャー受容体関与の細胞取り込み特性と酸性ムコ多糖類の体内分布の薬物動態学的解析" 薬学雑誌. 118(2). 51-71 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masami Haba et al.: "Macromolecule-macromolecule interaction in drug distribution. V.Effects of plasma proteins on uptake of fractionated [3H] heparin in isolated rat Kupffer cells." Biol.Pharm.Bull.19. 1352-1356 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano et al.: "Uptake Mechanism of Fractionated Heparin by Cultured Rat Parenchymal Liver Cells." Xenobio.Metabol.and Dispos.11. s94-95 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano et al.: "Kinetic characterization of binding and internalization of fractionated [3H] heparin in rat liver parenchymal cells in primary culture." Biol.Pharm.Bull.20. 680-683 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano et al.: "Internallization of fractionated ^3H-heparin by the scavenger-like receptor in rat liver parenchymal cells in promary culture." Drug Delivery. 4. 181-185 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masami Haba et al.: "Pharmacokinetic Analysis of Scavenger Receptor-Mediated Uptake of Mucopoly-saccharides in Various Cells." YAKUGAKU ZASSHI. 118. 51-71 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimihiko Urano, et al.: "Kinetic characterization of binding and internalization of fractionated ^3H-heparin in rat liver parenchymal cells in primary culture" Biol.Pharm.Bull.20 (6). 680-683 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kimihiko Urano, et al.: "Internalization of fractionated ^3H-heparin by the scavenger-like receptor in rat liver parenchymal cells in primary culture" Drug Delivery. 4. 181-185 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 巾正美, 渡辺淳: "スカベンジャー受容体関与の細胞取り込み特性と酸性ムコ多糖類の体内分布の薬物動態学的解析" 薬学雑誌. 118 (2). 51-71 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Jun Watanabe et al.: "Macromolecule-Macromolecule interaction in drug distuibution IV Molecu. lar dependency in interaction of fractionated ^3H-heparin with plasma protein" Biologieal Phavmaceutical Bulletin. 19 (2). 287-290 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Jun Watanabe et al.: "Uptake mechanism of fnactionated 〔^3H〕 heparin in isolated rat Kupffer cells : Invalvement of scavengen receptors" Biol. Pharm. Bull.19 (4). 581-586 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masami Haba et al.: "Molecular weight deperdency in the uptake of fractionated 〔^3H〕 heparin in isolated rat Kupffer cells" Biol. Pharm. Bull.19 (6). 864-868 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masami Haba et al.: "Macromolecule-Macromalecaule interaction indrug distribution. V. Effects of plasma protein son uptake of fractioneted 〔^3H〕 heparin in isolated rat Kupffer cells" Biol. Pharm. Bull.19 (10). 1352-1356 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 浦野公彦 他: "ラット肝実質細胞における分画heparinの輸送機構:スカベンジャー様受容体の関与" 薬物動態誌. 11. 94-95 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田中千尋 他: "ラット腹腔マクロファージにおける酸性ムコ多糖類の取り込み機構の速度論的検討" 薬物動態誌. 11. 150-150 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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