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2008 Fiscal Year Annual Research Report

ヒト薬物トランスポートソームの発現プロファイル構築に基づく薬物動態学的意義の解明

Research Project

Project/Area Number 20056018
Research InstitutionKyoto University

Principal Investigator

乾 賢一  Kyoto University, 医学研究科, 教授 (70034030)

Co-Investigator(Kenkyū-buntansha) 桂 敏也  京都大学, 医学研究科, 准教授 (10283615)
本橋 秀之  京都大学, 医学研究科, 助教 (30359822)
Keywords薬物トランスポータ / トランスポートソーム / 発現プロファイル / 遺伝子多型 / 薬物動態 / ヒト組織
Research Abstract

我々はこれまで、ヒト臨床検体における薬物トランスポータの発現プロファイルや遺伝子多型と薬物動態との相関について検討を進めてきた。しかし、その発現変動や遺伝子多型では説明できない薬物体内動態の個体差が依然認められるととなどから、何らかの制御因子も考慮に入れる必要があるものと考えられた。そこで本研究では、ヒト組織における発現および遺伝子解析の対象を薬物トランスポータのみならずそのトランスポートソーム構成因子に拡大し、検討を行うこととした。また、薬物・トランスポータに関してもこれまでの腎臓、消化管における検討に加え、肝臓における発現プロラァイル構築を行った。さらに、薬物トランスポータ遺伝子のプロモーター領域における遺伝子多型(rSNP)と薬物トランスポータ発現量との関連について解析を行った。その結果、腎臓の有機力,チオントランスポータOCT2のプロモーター活性が低下するrSNPを見いだし、この多型を有するヒトではOCT2の発現が低下する傾向が認めちれた。また、OCT2の腎特異的な発現が、DNAのメチル化によって制御されていることを明らかにした。現在、腎臓における既知のトランスポートソーム構成因子の発現プロファイル構築を進めて,いるところである。今後薬物トランスポータ発現量との相関解析や、トランスポートソーム構成因子の遺伝子多型解析を並行して進めることで、薬物トランスポートソームの分子機構を解明し、その薬物動態学的意義を明確にしたいと考えている。

  • Research Products

    (20 results)

All 2009 2008 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (8 results) Remarks (1 results)

  • [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

    • Peer Reviewed
  • [Journal Article] Involvement of human multidrug and toxin extrusion 1 in the drug interactionbetween cimetidine and metformin in renal epithelial cells2009

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

      Journal of- Pharmacology and Experimental Therapeutics 329

      Pages: 185-191

    • Peer Reviewed
  • [Journal Article] Targeted disruption of the multidrug and toxin extrusion 1 (Matel) genein mice reduces renal secretion of metformin2009

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

      Moledular Pharmacology (印刷中)

    • 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

    • 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

      Pages: 165-170

    • Peer Reviewed
  • [Journal Article] Adaptive responses of renal organic anion transporter 3 (OAT3) duringcholestasis2008

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

      American Journal of PhysiOlogy Renal Physiology 295

      Pages: 247-252

    • Peer Reviewed
  • [Journal Article] Regulatory mechanism governing the diurnal rhythm of intestinal H+/peptide cotransporter 1 (PEPT1)2008

    • Author(s)
      Hirofuthi Saito et.al.
    • Journal Title

      American Journal of Physiology Gastrointestinal and Liver Physiology 295

      Pages: 395-402

    • Peer Reviewed
  • [Journal Article] Identification and functional characterization of a novel human and ratriboflavin transporter. RFT12008

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

      American Journal of Physiology Cell Physiology 295

      Pages: 632-641

    • Peer Reviewed
  • [Journal Article] Transcellular transport of organic cation§ in double-transfected MDCK:cellsexpressing human organic cation transporters hOCT1/hMATE1-and HOCT2/hMATE12008

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

      Biochemical Pharmacology 76

      Pages: 894-903

    • 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

    • Peer Reviewed
  • [Journal Article] Regulation of basal core promoter activity of human organic cationtransporter 1 (OCT1/SLC22A1)2008

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

      American Journal of Physiology Gastrointestinal-and Liver Physiology 295

      Pages: 1211-1216

    • Peer Reviewed
  • [Presentation] Thirty year's advances in drug transporters -evolution from de factstandard-2008

    • Author(s)
      Ken-ichi.Inui
    • Organizer
      2008 American Association of Pharmaceutical Scientists Annual Meeting and Exposition
    • Place of Presentation
      Atlanta. U.S.A
    • Year and Date
      2008-11-18
  • [Presentation] Regulation of kidney-specific expression of human organic cationtransporter 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
  • [Presentation] Comparison of functional characteristics of H+/organic cationantiporters 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
  • [Presentation] Transcriptome analysis using purified proximal tubules in progressiverenal 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
  • [Presentation] rSNP analyses of organic ion transporters in the kidney2008

    • Author(s)
      Keri-OgaSawara et.al.
    • Organizer
      The IXth World Conference on Clinical Pharmacology and Therapeutics
    • Place of Presentation
      Quebec, Canada
    • Year and Date
      2008-07-29
  • [Presentation] Drug transporters : from bench to bedside2008

    • Author(s)
      Kenichi Inui
    • Organizer
      International Society for the Study of Xenobiotics 2nd AsianPacific Regional Meeting
    • Place of Presentation
      Shanghai, People's Republic of China
    • Year and Date
      2008-05-11
  • [Presentation] Pathophysiological roles of renal organic anion transporter 3 (OATS) inthe cholestasis2008

    • Author(s)
      Tomohiro Terada et.al.
    • Organizer
      International Society for the Study of Xenobiotics 2nd Asian Pacific Regional Meeting
    • Place of Presentation
      Shanghai, People's Republic of China
    • Year and Date
      2008-05-11
  • [Presentation] Pharmacogenomics of SLC22A/OCT, OAT and SLC47A/MATE drug transporters2008

    • Author(s)
      Ken-ichi Inui
    • Organizer
      2008 International Conference on Pharmacogenomics
    • Place of Presentation
      Busan, Korea
    • Year and Date
      2008-04-10
  • [Remarks]

    • URL

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

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Published: 2010-06-11   Modified: 2016-04-21  

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