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2013 Fiscal Year Final Research Report

Analysis of low temperature tolerance of membrane transporters and development of pan-transporter inhibitors

Research Project

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Project/Area Number 23659081
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionHiroshima University

Principal Investigator

TAKANO Mikihisa  広島大学, 医歯薬保健学研究院(薬), 教授 (20211336)

Co-Investigator(Renkei-kenkyūsha) YUMOTO Ryoko  広島大学, 大学院・医歯薬保健学研究院, 助教 (70379915)
Project Period (FY) 2011 – 2013
Keywords薬物動態 / 生体膜輸送 / トランスポーター / 低温忍容性 / 汎トランスポーター阻害剤
Research Abstract

Low temperature tolerance of membrane transporters, a characteristic showing transport activity even at ice-cold temperature, was examined in human erythrocytes and cultured cancer cells. A facilitative glucose transporter GLUT1 and a facilitative nucleoside transporter ENT1 showed marked low temperature tolerance in erythrocyte membrane vesicles. A secondary active monocarboxylate transporter MCT1 showed low temperature tolerance in erythrocytes. In addition, GLUT1 in culture cells such as A549 and HepG2 also showed low temperature tolerance.
In order to evaluate the function of these transporters properly, I attempted to develop novel pan-transporter inhibitors (stop and washing solutions for transport study). Among various reagents tested, solutions containing urea plus formaldehyde and 2-mercaptoethanol plus glutaraldehyde were found to be effective pan-transporter inhibitors in both membrane vesicle and culture cell studies.

  • Research Products

    (17 results)

All 2013 2012 2011 2010

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Book (1 results)

  • [Journal Article] Characterization of protamine uptake by opossum kidney epithelial cells2013

    • Author(s)
      Nagai, J., Komeda, T., Katagiri, Y., Yumoto, R. and Takano, M.
    • Journal Title

      Biol. Pharm. Bull

      Volume: 36(12) Pages: 1942-1949

    • DOI

      10.1248/bpb.b13-00553

    • Peer Reviewed
  • [Journal Article] Expression and function of PEPT2 during transdifferentiation of alveolar epithelial cells2013

    • Author(s)
      Takano, M., Horiuchi, T., Sasaki, Y., Kato, Y., Nagai, J. and Yumoto R.
    • Journal Title

      Life Sciences

      Volume: 93 Pages: 630-636

    • DOI

      10.1016/j.lfs.2013.08.008

    • Peer Reviewed
  • [Journal Article] Transport of biguanides by human organic cation transporter OCT22013

    • Author(s)
      Sogame, Y., Kitamura, A., Yabuki, M., Komuro, S. and Takano, M
    • Journal Title

      Biomed. Pharmacother

      Volume: 67 Pages: 425-430

    • DOI

      10.1016/j.biopha.2013.02.003

    • Peer Reviewed
  • [Journal Article] Effect of protamine on gentamicin accumulation in opossum kidney epithelial cells2013

    • Author(s)
      Nagai, J., Komeda, T., Yumoto, R. and Takano, M.
    • Journal Title

      J. Pharm. Pharmacol

      Volume: 65 Pages: 441-446

    • DOI

      10.1111/jphp.12005

    • Peer Reviewed
  • [Journal Article] Gadolinium modulates gentamicin uptake via an endocytosisindependent pathway in HK-2 human renal proximal tubular cell line. Eur2012

    • Author(s)
      Sawada, T., Nagai, J., Okada, Y., Yumoto, R. and Takano, M
    • Journal Title

      J. Pharmacol

      Volume: 684(1-3) Pages: 146-153

    • DOI

      10.1016/j.ejphar.2012.03.030

    • Peer Reviewed
  • [Journal Article] Megalin/cubilin-mediated uptake of FITC-labeled IgG by OK kidney epithelial cells2011

    • Author(s)
      Nagai, J., Sato, K., Yumoto, R. and Takano, M
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 26 (5) Pages: 474-485

    • DOI

      10.2133/dmpk.DMPK-11-RG-022

    • Peer Reviewed
  • [Presentation] 生体膜輸送研究のための新たな輸送反応停止液の探索・開発2013

    • Author(s)
      平林悠, 今岡大明, 永井純也, 湯元良子, 高野幹久
    • Organizer
      膜シンポジウム2013
    • Place of Presentation
      京都市
    • Year and Date
      20131107-08
  • [Presentation] 氷冷下におけるグルコーストランスポーターの機能2013

    • Author(s)
      平林悠, 今岡大明, 永井純也, 湯元良子, 高野幹久
    • Organizer
      第35回日本膜学会年会
    • Place of Presentation
      東京都
    • Year and Date
      20130520-21
  • [Presentation] 生体膜と人工膜の研究融合のための相互理解に向けて2013

    • Author(s)
      高野幹久
    • Organizer
      第35回日本膜学会年
    • Place of Presentation
      東京都
    • Year and Date
      20130520-21
  • [Presentation] 哺乳類トランスポーターの低温忍容性の解明2012

    • Author(s)
      今岡大明, 平林悠, 永井純也, 湯元良子, 高野幹久
    • Organizer
      第34回生体膜と薬物の相互作用ジンポジウム
    • Place of Presentation
      京都市
    • Year and Date
      20121115-16
  • [Presentation] 氷冷下におけるヒトのトランスポーター機能2011

    • Author(s)
      高野幹久, 鈴木聡, 今岡大明, 永井純也, 湯元良子
    • Organizer
      膜シンポジウム2011
    • Place of Presentation
      沖縄市
    • Year and Date
      20111118-19
  • [Presentation] 哺乳類トランスポーターの低温忍容性とその普遍性に関する検討2011

    • Author(s)
      今岡大明, 鈴木聡, 永井純也, 湯元良子, 高野幹久
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京
    • Year and Date
      20110529-31
  • [Presentation] ヒト赤血球膜トランスポーターの低温忍容性2011

    • Author(s)
      湯元良子, 鈴木聡, 今岡大明, 永井純也, 高野幹久
    • Organizer
      日本膜学会第33年会
    • Place of Presentation
      東京都
    • Year and Date
      20110512-13
  • [Presentation] Human transporters that function at ice-cold temperature - Important notice for transporter research2010

    • Author(s)
      Takano, M., Suzuki, S., Imaoka, H., Nagai, J. and Yumoto, R.
    • Organizer
      ISSX 9th International Meeting Istanbul 2010
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      20100904-08
  • [Presentation] ヒト赤血球膜の促進拡散トランスポーターは氷冷下でも機能する ~薬物相互作用研究上の留意点~2010

    • Author(s)
      鈴木聡, 湯元良子, 今岡大明, 永井純也, 高野幹久
    • Organizer
      医療薬学フォーラム2010
    • Place of Presentation
      広島市
    • Year and Date
      20100710-11
  • [Presentation] トランスポーターの低温忍容性とトランスポーター阻害薬探索研究上の留意点に関する考察2010

    • Author(s)
      高野幹久, 鈴木聰, 木村衣里, 今岡大明, 永井純也, 湯元良子
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島市
    • Year and Date
      20100512-14
  • [Book] 薬物排泄実験・腎排泄, 「薬剤学実験法必携マニュアル」2013

    • Author(s)
      高野幹久, 南江堂
    • Total Pages
      194-204
    • Publisher
      日本薬剤学会出版委員会

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Published: 2015-06-25  

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