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Pharmacokinetic Study on Mucopolysaccharide : Effect of Plasma Protein on the Hepatic Uptake of fractionated Heparin

Research Project

Project/Area Number 04671328
Research Category

Grant-in-Aid for General Scientific Research (C)

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) HABA Masami  Nagoya City University, Faculty of Pharmaceut. sci. Assoc. Professor, 薬学部, 助手 (70254307)
YUASA Hiroaki  Nagoya City University, Faculty of Pharmaceut. sci. Assoc. Professor, 薬学部, 助教授 (20191471)
林 弥生  名古屋市立大学, 薬学部, 助手 (00117847)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsrat parenchymal hepatocyte / fractionated heparin / dose-dependent uptake / transport inhibitor / anion transport system / plasma protein / a-globulin / albumin / alpha-グロブリン / 血清アルブミン
Research Abstract

(1) The uptake rate of fractionated [^3H]heparin by rat parenchymal hepatocytes was concentration-dependent and found to be expressed by a Michaelis-Memten equation.
(2) The uptake was not inhibited by the inhibitor of receptor-mediated endocytosis, pohenylarsine oxide, but it was inhibited hoth by an inhibitor of the anion transprtt system, DIDS and by an anion, rose bengal.
(3) Interelization o ffractionnated heparin was confirmed with FITC-fractionated heparin using confocal imaging wywtem with an inverted flurorescence microscope.
(4) After intravenous administration of fractionated [^3H]heparin the uptake rates of radioactivity by parenchymal non-parenchymal cells were dose-dependent, and the dose-dependency was more remarkable in the uptake by non-parenchymal cells.
(5) The uptake clearances for both parenchymal and non-parenchymal cells were considerablly larger than that for PVP(polyvinylpyrorifon), suggesting that the fractionated peparin was taken up by the other mechaniasm than fluid phase encocytosis.
(6) The interaction of fractionated [^3H]heparin with a-globulin was greater than that with albumin.
(7) a-Globulin showed the decreasing effect on the hepatic uptake clearance of fractionated [^3H]heparin in the perfused rat liver, and "protein-mediated transport" was involved in the uptake. On the other hand albumin did not affect the uptake process.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Jun Watanabe et al.: "Uptake Mechanism of Fractionated[^3H]Heparin in Rat Parenchymal Hepatocytes in Primary Culture:Effect of Transport Inhibitors on the Uptake" Biol.Pharm.Bull.16. 497-500 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Uptake of Fluorescein Isothiocyanote(FITC)-Fractionated Heparin by Rat Parenchymal Hepatocytes in Primary Culture" Biol.Pharm.Bull.16. 939-941 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Dose-Dependent Uptake of Radioactivity by Liver Parenchymal and Non-Parenchymal Cells after Introvenous Administration of Fractionated ^3H-Heparin to Rats" Biol.Pharm.Bull.16. 1031-1034 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Macromolecule-Macromolecule Interaction in Drug Distribution III Kinetic Characterization of the Uptake of Fractionated[^3H]Heparin and the Effect of Plasma Proteins in Perfused Rat Liver" Biol.Pharm.Bull.16. 1035-1039 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Uptake Mechanism of Fractionated [^3H]heparin in rat Parenchymal Hepatocytes iPrimary Culrure : Effect of Transport Inhibitors on the Uptake" Biol. Pharm. Bull. 16. 497-500 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Uptake of Fluorescein Isothiocyanate (FITC)Fractionated Herarin by Rat Parenchymal Hepatocytes in Priamry Culture" Biol. Pharm. Bull. 16. 1031-1034 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Macromolecule-Macromolecule Ineraction in drug Distribution. III.Kinetic Characterization o fthe Uptake of Fractionated [^3H]heparin and th eEffect of Plasma Proteins in the Perfused Rat Liver" Biol. Pharm. Bull. 16. 1035-1039

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jun Watanabe et al.: "Uptake Mechanism of Fractionated [^3H] heparin in Rat Parenchymal Hepatocytein Primary culture:Effect of Transport Inhibitors on the Uptake" Boil,Pharm,Bull.16. 497-500 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Watanabe et al.: "Uptake of Fluorescein Isothisopnate(FITC)-Fractionated Heparin by Rat Parerchymal Hepatocytes in Primary Culture" Biol.Pharm.Bull.16. 939-941 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Watanabe et al.: "Dose-Deperdent Uptake of Ratioactivity by Parendrymal and Non-pareuchymal Cells often In Travenous Administvation of ^3H-Heparin" Biol.Pharm.Bull.16. 1031-1034 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Watanabe et al.: "Macromolecule Macvomolecule Interaction in Drug DistributionIII.Kivetic Charactenization of the Uptake of Rractionated 〔3H〕Heparin and the Effect of Plasure Proteins in the Perfused Rat Liven" Biol.Pharm.Bull.16. 1035-1039 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Jun Watanabe: "Uptake Mechanism of Fractionated [^3H]-Heparin in Rat Parenchymal Hepatocyte in Primary Culture:Effect of Transport Inhibitors on the Uptake" Biol,Pharm,Bull.(No.5). 16. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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