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A structure-relationship study of the transport mechanism of polyamine compounds across plasma membrane.

Research Project

Project/Area Number 07672414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

ISEKI Ken  Hokkaido Univ., Medical Hospital., Associate Professor, 医学部・附属病院, 助教授 (40203062)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordspolyamines / intestinal absorption / renal excretion / membrane transport / membrane potential / carrier protein / brush-border membrane / basolateral membrane / トリエンチン
Research Abstract

In this study, we investigated the structure-relationship of the transport mechanism of polycationic drugs (di-, tri-and tetraamine compounds) across plasma membrane using rat intestinal brush-border and basolateral membrane vesicles, and rat renal brush-border membrane vesicles.
1. Transport mechanism of polycationic drugs across intestinal brush-border membrane
A good correlation between the initial transport rate of diamine compounds and their lipophilicities. On the other hand, the transport rate of tri-and tetraamine compounds was almost same as diamine compound, although the lipophilicity of tri-and tetraamine were much lower than diamine compounds. A valinomycin induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds by membrane vesicles, and a good correlation was observed between the lipophilicity and the amount of diffusion-potential dependent transport of diamine compounds. However, because of their extremely lower lipophilici … More ty, tri-and tetraamine compounds werenot affected by the diffusion potential. Furthermore, membrane surface potential playd a common role in the transport of all polycationic compounds.
2. Transport mechanism of polycationic drugs across intestinal basolateral membrane
There was a specific carrier for putrescine, a diamine compound, in the ratintestinal basolateral membrane. The driving force of this carrier was an inward Na^+ gradient, and transport into the cell. Carrier-mediated transport of putrescine was inhibited by other diamine compounds. Because of that tri- and tetraamine compounds did not affect to the transport, this carrier would recognize only diamine compounds.
3. Transport mechanism of polycationic drugs across renal brush-border membrane
Because of spermine and trientine, tetraamine compounds, trans-stimulated the uptake of spermine by rat renal basolateral membrane vesicles, a specific carrier for tetraamine compounds existed in this membrane. Moreover, in-vitro study, the renal clearance of trientine was faster than creatinine clearance. These data suggest that this transport system contributes to the secretion of tetraamines in the kidney proximal tubule. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Michiya Kobayashi: "Sodium-dependent putrescine transport in rat intestinal basolateral menbrane" Pharmaceutical Sciences. 1. 337-339 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ryou Tanabe: "Uptake mechanism of trientine by rat intestinal brush-border menbrane vesicles" Journal of Pharmacy & Pharmacology. 48. 517-521 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi: "A structure-relationship study on the uptake of aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles" Journal of Pharmacy & Pharmacology. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi: "The mechanism of excretion of trientine from the rat kidney : Trientine is not recognized by the H^+/organic cation transporter" Journal of Pharmacy & Pharmacology. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi et al: "Sodium-dependent putrescine transport in rat intestinal basolateral membrane" Pharmaceutical Sciences. 1. 337-339 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ryou Tanabe et al: "Uptake mechanism of trientine by rat intestinal brush-border membrane vesicles" Journal of Pharmacy & Pharmacology. 48. 517-521 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi et al: "A structure-relationship study on the uptake of aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles" Journal of Pharmacy & Pharmacology. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi et al: "The mechanism of excretion of trientine from the rat kidney : Trientine is not recognized by the H^+/organic cation transporter" Journal of Pharmacy & Pharmacology. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Michiya Kobayashi: "A structure-relationship study on the uptake of aliphatic polymine compounds by rat intestinal brush-border membrane vesicles" Journal of Pharmacy & Pharmacology. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Michiya Kobayashi: "The mechanism of excretion of trientine from the rat kidney : Trientine is not recognized by the H^+/organic cation transporter" (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ryou Tanabe: "Uptake mechanism of trientine by rat intestinal brush-border membrane vesicles" Journal of Pharmacy & Pharmacology. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Michiya Kobayashi: "Sodium-dependent putrescine transport in rat intestinal basola teral membrane" Pharmaceutical Sciences. 1. 337-339 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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