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Identification of essential determinants for membrane localization of drug transporters and elucidation of their polarized transport mechanisms

Research Project

Project/Area Number 19590142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKyoto University

Principal Investigator

KATSURA Toshiya  Kyoto University, 医学研究科, 准教授 (10283615)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords極性上皮細胞 / 薬物トランスポータ / 膜輸送 / 薬物動態 / 有機カチオントランスポータ / 細胞膜ターゲティング
Research Abstract

腎臓の近位尿細管に局在する薬物の運び屋タンパク質(トランスポータ)がどのように細胞膜に運ばれ機能するか、またその発現量がどのように規定されているか等を明らかにすることを目的として検討を行い、腎臓における薬物輸送を再現するモデル細胞の構築に成功し、また薬物トランスポータの発現量を規定する因子を同定することができた。さらに、トランスポータを全く発現しないマウスを作製し、その役割を明確にした。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (59 results)

All 2009 2008 2007 Other

All Journal Article (34 results) (of which Peer Reviewed: 34 results) Presentation (23 results) Remarks (2 results)

  • [Journal Article] Targeted disruption of the multidrug and toxin extrusion 1 (matel) gene in mice reduces renal secretion of metformin2009

    • Author(s)
      Tsuda M, Terada T, Mizuno T, Katsura T, Shimakura J, Inui K.
    • Journal Title

      Mol.Pharmacol. 75

      Pages: 1280-1286

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells2009

    • Author(s)
      Tsuda M, Terada T, Ueba M, Sato T, Masuda S, Katsura T, Inui K.
    • Journal Title

      J.Pharmacol.Exp.Ther. 329

      Pages: 185-191

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity2009

    • Author(s)
      Kajiwara M, Terada T, Ogasawara K, Iwano J, Katsura T, Fukatsu A, Doi T, Inui K.
    • Journal Title

      J.Hum.Genet. 54

      Pages: 40-46

    • NAID

      10030728868

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity2009

    • Author(s)
      Moto Kajiwara, et al.
    • Journal Title

      Journal of Human Genetics 54

      Pages: 40-46

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformln in renal epithelial ceels2009

    • Author(s)
      Masahiro Tsuda, et al.
    • Journal Title

      Journal of Pharmacology and Exerimental Therapeutics 329

      Pages: 185-191

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted disruption of the multidrug and toxin extrusion 1 (Matel) gene in mice reduces renal secretion of metformin2009

    • Author(s)
      Masahiro Tsuda, et al.
    • Journal Title

      Molecular Pharmacology

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1).2008

    • Author(s)
      Kajiwara M, Terada T, Asaka J, Aoki M, Katsura T, Ikai I, Inui K.
    • Journal Title

      Am.J.Physiol.Gastrointest. Liver Physiol. 295

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE12008

    • Author(s)
      Sato T, Masuda S, Yonezawa A, Tanihara Y, Katsura T, Inui K.
    • Journal Title

      Biochem.Pharmacol. 76

      Pages: 894-903

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation2008

    • Author(s)
      Aoki M, Terada T, Kajiwara M, Ogasawara K, Ikai I, Ogawa O, Katsura T, Inui K.
    • Journal Title

      Am.J.Physiol.Renal Physiol. 295

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of regulatory polymorphisms in organic ion transporter genes (SLC22A) in the kidney2008

    • Author(s)
      Ogasawara K, Terada T, Motohashi H, Asaka J, Aoki M, Katsura T, Kamba T, Ogawa O, Inui K.
    • Journal Title

      J.Hum.Genet. 53

      Pages: 607-614

    • NAID

      10021249665

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thyroid hormone regulates the expression and function of P-glycoprotein in Caco-2 cells2008

    • Author(s)
      Naoki Nishio, et al.
    • Journal Title

      Pharmaceutical Research 25

      Pages: 1037-1042

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of regulatory polymorphisms in organic ion transporter genes (SLC22A) in the kidney2008

    • Author(s)
      Ken Ogasawara, et al.
    • Journal Title

      Journal of Human Genetics 53

      Pages: 607-614

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation2008

    • Author(s)
      Masayo Aoki, et al.
    • Journal Title

      American Journal of Physiology Renal Physiology 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis2008

    • Author(s)
      Jiarong Chen, et al.
    • Journal Title

      American Journal of Physiology Renal Physiology 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and functional characterization of a. novel human and rat riboflavin transporter, RFTl2008

    • Author(s)
      Atsushi Yonezawa, et al
    • Journal Title

      American Journal of Physiology Cell Physiology 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE12008

    • Author(s)
      Tomoko Sato, et al.
    • Journal Title

      Biochemical Pharmacology 76

      Pages: 894-903

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of organic cation transporter 3 (SLC22A3) expression for the cytotoxic effect of oxaliplatin in colorectal cancer2008

    • Author(s)
      Sachiko Yokoo, et al.
    • Journal Title

      Drug Metabolism and Disposition 36

      Pages: 2299-2306

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of basal core promoter activity of human organic cation transporter 1 (OCTl/SLC22Al)2008

    • Author(s)
      Moto Kajiwara, et al.
    • Journal Title

      American Journal of Physiology Gastrointestinal and Liver Physiology 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical roles of Spl in gene expression of human and rat H+/organic cation antiporter MATE12007

    • Author(s)
      Kajiwara M, Terada T, Asaka J, Ogasawara K, Katsura T, Ogawa O, Fukatsu A, Doi T, Inui K.
    • Journal Title

      Am.J.Physiol.Renal Physiol. 293

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity2007

    • Author(s)
      Yokoo S, Yonezawa A, Masuda S, Fukatsu A, Katsura T, Inui K.
    • Journal Title

      Biochem.Pharmacol. 74

      Pages: 477-487

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusion/H+-organic cation antiporters2007

    • Author(s)
      Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K.
    • Journal Title

      Biochem.Pharmacol. 74

      Pages: 359-371

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of essential histidine and cysteine residues of the H+/organic cation antiporter multidrug and toxin extrusion (MATE)2007

    • Author(s)
      Asaka J, Terada T, Tsuda M, Katsura T, Inui K.
    • Journal Title

      Mol.Pharmacol. 71

      Pages: 1487-1493

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the basal promoter element of human organic cation transporter 2 gene2007

    • Author(s)
      Asaka J, Terada T, Ogasawara K, Katsura T, Inui K.
    • Journal Title

      J.Pharmacol.Exp.Ther. 321

      Pages: 684-689

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure rats2007

    • Author(s)
      Nishihara K, Masuda S, JiL, Katsura T, Inui K.
    • Journal Title

      Biochem.Pharmacol. 73

      Pages: 1482-1490

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members(hOAT1, hOAT3, and hOCT2)2007

    • Author(s)
      Yuichi Uwai, et. al.
    • Journal Title

      Pharmaceutical Research 24巻

      Pages: 811-815

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of the basal promoter element of human organic cation transporter 2 gene2007

    • Author(s)
      Jun-ichi Asaka, et. al.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 321巻

      Pages: 684-689

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure2007

    • Author(s)
      Kumiko Nishihara, et. al.
    • Journal Title

      Biochemical Pharmacology 73巻

      Pages: 1482-1490

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of essential histidine and cysteine residues of the H^+/organic cation antiporter multidrug and toxin extrusion(MATE)2007

    • Author(s)
      Jun-ichi Asaka, et. al.
    • Journal Title

      Molecular Pharmacology 71巻

      Pages: 1487-1493

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte nuclear factor-4α regulates the human organic anion transporter 1 gene in the kidney2007

    • Author(s)
      Ken Ogasawara, et. al.
    • Journal Title

      American Journal of Physiology Renal Physiology 292巻

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction and transport of mycophenolic acid and its glucuronide via human organic anion transporters hOAT1 and hOAT32007

    • Author(s)
      Yuichi Uwai, et. al.
    • Journal Title

      Biochemical Pharmacology 74巻

      Pages: 161-168

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusion/H^+-organic cation antiporters2007

    • Author(s)
      Yuko Tanihara, et. al.
    • Journal Title

      Biochemical Pharmacology 74巻

      Pages: 359-371

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cl-dependent upregulation of human organic anion transporters: different effects on transport kinetics between hOAT1 and hOAT32007

    • Author(s)
      Harumasa Ueo, et. al.
    • Journal Title

      American Journal of Physiology Renal Physiology 293巻

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity2007

    • Author(s)
      Sachiko Yokoo, et. al.
    • Journal Title

      Biochemical Pharmacology 74巻

      Pages: 477-487

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical roles of Sp1 in gene expression of human and rat H^+/organic cation antiporter MATE12007

    • Author(s)
      Moto Kajiwara, et. al.
    • Journal Title

      American Journal of Physiology Renal Physiology 293巻

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Comparison of functional characteristics of H+/organic cation antiporters MATE1 and MATE2-K2008

    • Author(s)
      Tsuda M, et al.
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, USA.
    • Year and Date
      2008-11-18
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) by DNA methylation2008

    • Author(s)
      Ogasawara K, et al.
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2008-11-18
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) by DNA methylation2008

    • Author(s)
      Ken Ogasawara, et al.
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, U.S.A.
    • Year and Date
      2008-11-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] Comparison of functional characteristics of H+/organic cation antiporters MATE1 and MATE2-K2008

    • Author(s)
      Masahiro Tsuda, et al.
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, U.S.A.
    • Year and Date
      2008-11-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] Transcriptome analysis using purified proximal tubules in progressive renal failure rats2008

    • Author(s)
      Kumiko Nishihara, et al.
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta, U.S.A.
    • Year and Date
      2008-11-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒトMATE1の機能的発現における翻訳後プロセシングの重要性2008

    • Author(s)
      岩野淳子, ら
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本市
    • Year and Date
      2008-10-31
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒトMTE1の機能的発現における翻訳後プロセシングの重要性2008

    • Author(s)
      岩野淳子, ら
    • Organizer
      第23回日本薬物動態学会年会
    • Place of Presentation
      熊本市
    • Year and Date
      2008-10-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] Pathophysiological roles of renal organic anion transporter 3 (OAT3) in the cholestasis2008

    • Author(s)
      Tomohiro Terada, et al.
    • Organizer
      International Society for the Study of Xenobiotics 2nd Pacific Asian Regional Meeting
    • Place of Presentation
      Shanghai, People's Republic of China
    • Year and Date
      2008-05-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Promoter analyses of human and rat H+/organic cation antiporter (MATE1)2007

    • Author(s)
      Kajiwara M, et al.
    • Organizer
      8th International Society for the Study Xenobiotics International Meeting
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2007-10-10
    • Related Report
      2008 Final Research Report
  • [Presentation] Promoter analyses of human and rat H^+/organic cation antiporter (MATE1)2007

    • Author(s)
      Moto Kajiwara, et. al.
    • Organizer
      8th International Society for the Study Xenobiotics International Meeting
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2007-10-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] Expressional and functional changes in rat H+/organic cation antiporter MATE1 in chronic renal failure2007

    • Author(s)
      Nishihara K, et al.
    • Organizer
      Biomedical Transporters 2007
    • Place of Presentation
      Bem, Switzerland
    • Year and Date
      2007-08-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Structural characteristics and substrate specificity of hMATE2-K2007

    • Author(s)
      Tanihara Y, et al.
    • Organizer
      Biomedical Transporters 2007
    • Place of Presentation
      Bern, Switzerland
    • Year and Date
      2007-08-13
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Expressional and functional changes in rat H^+/organic cation antiporter MATE1 in chronic renal failure2007

    • Author(s)
      Kumiko Nishihara, et. al.
    • Organizer
      Biomedical Transporters 2007
    • Place of Presentation
      Bern, Switzerland
    • Year and Date
      2007-08-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] OCT and Mate families are key transporters in platinum agents-induced nephrotoxicity2007

    • Author(s)
      Yokoo S, et al.
    • Organizer
      4th World Conference on Drug Absorption, Transport and Delivery
    • Place of Presentation
      Kanazawa, Japan
    • Year and Date
      2007-06-21
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Drug-drug interaction and its importance for the safe and effective pharmacotherapy2007

    • Author(s)
      Katsura T, et al.
    • Organizer
      4th World Conference on Drug Absorption, Transport and Delivery
    • Place of Presentation
      Kanazawa, Japan
    • Year and Date
      2007-06-20
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] hOCT/hMATEダブルトランスフエクタントの構築と経細胞輸送解析2007

    • Author(s)
      佐藤朋子, ら
    • Organizer
      日本薬剤学会第22年会
    • Place of Presentation
      さいたま市
    • Year and Date
      2007-05-22
    • Related Report
      2008 Final Research Report
  • [Presentation] hOCT/hMATEダブルトランスフェクタントの構築と経細胞輸送解析2007

    • Author(s)
      佐藤朋子, ら
    • Organizer
      日本薬剤学会第22年会
    • Place of Presentation
      さいたま市
    • Year and Date
      2007-05-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Functional roles of cystein and histidine residues in rat H+/organic cation antiporter MATE12007

    • Author(s)
      Terada T, et al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-25
    • Related Report
      2008 Final Research Report
  • [Presentation] Identification of a driving force of H+/organic cation antiporter rat and human MATE1 using plasma membrane vesicles2007

    • Author(s)
      Tsuda M, et al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-25
    • Related Report
      2008 Final Research Report
  • [Presentation] Functional roles of cystein and histidine residues in rat H^+/organic cation antiporter MATE12007

    • Author(s)
      Tomohiro Terada, et. al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] Identification of a driving force of H^+/organic cation antiporter rat and human MATE1 using plasma membrane vesicles2007

    • Author(s)
      Masahiro Tsuda, et. al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] Regulatory mechanisms for gene expression of human organic anion transporters2007

    • Author(s)
      Ken Ogasawara, et. al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] Transcriptional activation of MDR1 gene by thyroid hormone receptor2007

    • Author(s)
      Toshiya Katsura, et. al.
    • Organizer
      Pharmaceutical Sciences World Congress 2007
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2007-04-24
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~yakuzai/kenky.html

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~yakuzai/kenky.html

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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