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

Research Project

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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 / 薬学 / 膜小胞 / 輸送阻害剤 / 培養細胞 / GLUT / 生体膜輸送研究 / 赤血球膜小胞 / 腎刷子縁膜小胞 / ENT / MCT
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2014 2013 2012 2011 2010

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Characterization of Protamine Uptake by Opossum Kidney Epithelial Cells2013

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

      Biological and Pharmaceutical Bulletin

      Volume: 36 Issue: 12 Pages: 1942-1949

    • DOI

      10.1248/bpb.b13-00553

    • NAID

      130003382061

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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 Issue: 17 Pages: 630-636

    • DOI

      10.1016/j.lfs.2013.08.008

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 5 Pages: 425-430

    • DOI

      10.1016/j.biopha.2013.02.003

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of protamine on gentamicin accumulation in opossum kidney epithelial cells.2013

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

      J Pharm Pharmacol

      Volume: 65 Issue: 3 Pages: 441-446

    • DOI

      10.1111/jphp.12005

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Flow Cytometry Analysis of Cancer Cell Death Induced by the Extract of Thai Plant <i>Ellipeiopsis cherrevensis</i>2013

    • Author(s)
      Ryoko Yumoto
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 28 Issue: 2 Pages: 159-163

    • DOI

      10.2133/dmpk.DMPK-12-NT-056

    • NAID

      130004933522

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gadolinium modulates gentamicin uptake via an endocytosis-independent pathway in HK-2 human renal proximal tubular cell line.2012

    • Author(s)
      Takeshi Sawada
    • Journal Title

      European Journal of Pharmacology

      Volume: 84(1-3) Issue: 1-3 Pages: 146-153

    • DOI

      10.1016/j.ejphar.2012.03.030

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of cigarette smoke extract on insulin transport in alveolar epithelial cell line A5492012

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

      Lung

      Volume: 190 Issue: 6 Pages: 651-659

    • DOI

      10.1007/s00408-012-9413-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhancement Effect of Poly(amino acid)s on Insulin Uptake in Alveolar Epithelial Cells2012

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

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 6 Pages: 570-578

    • DOI

      10.2133/dmpk.DMPK-12-RG-002

    • NAID

      130004933511

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endocytic Uptake of FITC-albumin by Human Alveolar Epithelial Cell Line A5492012

    • Author(s)
      Yumoto, R., Suzuka, S., Oda, K., Imaoka, H. and Nagai, J. and Takano, M.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 3 Pages: 336-343

    • DOI

      10.2133/dmpk.DMPK-11-RG-127

    • NAID

      130004463255

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Megalin/Cubilin-mediated Uptake of FITC-labeled IgG by OK Kidney Epithelial Cells2011

    • Author(s)
      Junya Nagai, Koya Sato, Ryoko Yumoto, Mikihisa Takano
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 26 Issue: 5 Pages: 474-485

    • DOI

      10.2133/dmpk.DMPK-11-RG-022

    • NAID

      130004463211

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 生体膜トランスポーターの低温忍容性とそれを考慮した新たな汎輸送反応停止液の開発2014

    • Author(s)
      平林 悠、永井純也、湯元良子、高野幹久
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮ソニックビル
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] 人工膜研究者のための生体膜輸送の基礎講座2013

    • Author(s)
      高野幹久
    • Organizer
      日本膜学会第35年会
    • Place of Presentation
      早稲田大学西早稲田キャンパス
    • Related Report
      2013 Annual Research Report
    • Invited
  • [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
      日本膜学会第35年会
    • Place of Presentation
      早稲田大学西早稲田キャンパス
    • Related Report
      2013 Annual Research Report
  • [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
      京都府立医科大学
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Organizer
      第34回生体膜と薬物の相互作用ジンポジウム
    • Place of Presentation
      京都大学薬学部
    • Related Report
      2012 Research-status Report
  • [Presentation] Effect of D-glucose on insulin uptake in human alveolar epithelial cell line A5492012

    • Author(s)
      Keisuke Oda
    • Organizer
      27th JSSX Annual Meeting in Tokyo
    • Place of Presentation
      Tower Hall Funabori(東京都)
    • Related Report
      2012 Research-status Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [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
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      東京都
    • Related Report
      2011 Research-status Report
  • [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
    • Organizer
      膜シンポジウム2011
    • Place of Presentation
      宜野湾市(沖縄)
    • Related Report
      2011 Research-status Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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
    • Publisher
      日本薬剤学会出版委員会
    • Related Report
      2013 Final Research Report
  • [Book] 薬剤学実験法必携マニュアル2013

    • Author(s)
      高野幹久(日本薬剤学会出版委員会編)
    • Total Pages
      423
    • Publisher
      南工堂
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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