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Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

Research Project

Project/Area Number 23590180
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionMie University

Principal Investigator

OKUDA Masahiro  三重大学, 医学部附属病院, 教授 (70252426)

Co-Investigator(Kenkyū-buntansha) IWAMOTO Takuya  三重大学, 医学部附属病院, 准教授 (30447867)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsメトトレキサート / リポ多糖 / ラット / 有機アニオントランスポータ / 腎クリアランス / サイトカイン / リポポリサッカライド / 腎尿細管 / 尿細管分泌 / 炎症 / 尿細管分泌クリアランス
Research Abstract

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.

Report

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

    (18 results)

All 2014 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 8 results) Presentation (8 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions: Implication for intestinal barrier function2014

    • Author(s)
      Ikemura K, Iwamoto T, Okuda M
    • Journal Title

      Pharmacol Ther

      Volume: 143 Issue: 2 Pages: 217-224

    • DOI

      10.1016/j.pharmthera.2014.03.002

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chracteristics of pemetrexed transport by renal basolateral organic anion transporter hOAT32014

    • Author(s)
      Kurata T, Iwamoto T, Kawahara Y, Okuda M
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 29(2) Pages: 148-153

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Altered pharmacokinetics of cimetidine caused by down-regulation of renal rat organic cation transporter 2 (rOCT2) after liver ischemia-reperfusion injury2013

    • Author(s)
      Ikemura K, Nakagawa E, Kurata K, Iwamoto T, Okuda M
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 28(6) Pages: 504-509

    • NAID

      130004463334

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-145 post-transcriptionally regulates the expression and function of P-glycoprotein in intestinal epithelial cells2013

    • Author(s)
      Ikemura K, Yamamoto M, Miyazaki S, Mizutani H, Iwamoto T, Okuda M
    • Journal Title

      Mol Pharmacol

      Volume: 83(2) Pages: 399-405

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-145 post-transcriptionally regulates the expression and function of P-glycoprotein in intestinal epithelial cells.2013

    • Author(s)
      Ikemura et al.
    • Journal Title

      Mol Pharmacol.

      Volume: 83 Issue: 2 Pages: 399-405

    • DOI

      10.1124/mol.112.081844

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine2012

    • Author(s)
      Ikemura K, Inoue K, Mizutani H, Oka H, Iwamoto T, Okuda M
    • Journal Title

      Eur J Pharmacol

      Volume: 690(1-3) Pages: 192-201

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of basophil CD203c as a predictor of carboplatin-related hypersensitivity reaction in patients with gynecologic cancer2012

    • Author(s)
      Iwamoto T, Yuta A, Tabata T, Sugimoto H, Gabazza EC, Hirai H, Kojima S, Okuda M
    • Journal Title

      Biol Pharm Bull

      Volume: 35(9) Pages: 1487-1495

    • NAID

      130001872071

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of basophil CD203c as a predictor of carboplatin-related hypersensitivity reaction in patients with gynecologic cancer.2012

    • Author(s)
      Iwamoto et al.
    • Journal Title

      Biol Pharm Bull.

      Volume: 35 Pages: 1487-1495

    • NAID

      130001872071

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An antioxidant Trolox restores decreased oral absorption of cyclosporine A after liver ischemia-reperfusion through distinct mechanisms between CYP3A and P-glycoprotein in the small intestine.2012

    • Author(s)
      Ikemura et al.
    • Journal Title

      Eur J Pharmacol.

      Volume: 690 Issue: 1-3 Pages: 192-201

    • DOI

      10.1016/j.ejphar.2012.06.031

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] miR-145による小腸上皮細胞P-糖蛋白質の転写後発現調節機構2013

    • Author(s)
      池村健治、山本弥里、宮崎さおり、水谷秀樹、岩本卓也、奥田真弘
    • Organizer
      第59回日本薬学会東海支部総会・大会
    • Place of Presentation
      名城大学八事キャンパス(名古屋市)
    • Year and Date
      2013-07-06
    • Related Report
      2013 Final Research Report
  • [Presentation] miR-145 による小腸上皮細胞P-糖蛋白質の転写後発現調節機構2013

    • Author(s)
      池村健治、山本弥里、宮崎さおり、水谷秀樹、岩本卓也、奥田真弘
    • Organizer
      第59回日本薬学会東海支部総会・大会
    • Place of Presentation
      名古屋市
    • Related Report
      2013 Annual Research Report
  • [Presentation] miR-145は小腸上皮細胞P-糖蛋白質の発現・機能調節に関与する2012

    • Author(s)
      池村健治、山本弥里、宮崎さおり、水谷秀樹、岩本卓也、奥田真弘
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸市
    • Year and Date
      2012-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] ペメトレキセドの尿細管分泌機構における有機アニオントランスポーター3の役割2012

    • Author(s)
      倉田朋彦、岩本卓也、河原佑樹、奥田真弘
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2012-03-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝虚血再灌流障害時のCyclosporine Aの経口bioavailability低下における酸化ストレスの役割2012

    • Author(s)
      池村健治
    • Organizer
      日本薬剤学会年会第26年会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 虚血再灌流障害時における酸化ストレスを介した小腸CYP3A及びP-糖蛋白質の発現上昇によるcyclosporine Aの経口吸収低下2011

    • Author(s)
      池村健治、水谷秀樹、岩本卓也、奥田真弘
    • Organizer
      第5回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      名古屋大学医学部附属病院(名古屋市)
    • Year and Date
      2011-11-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Pathophysiological Role of Chenodeoxycholic Acid on Hepatic Disposition of Metformin via Organic Cation Transporter 1 in Acute Cholestasis2011

    • Author(s)
      Tomohiko Kurata, Yuichi Muraki, Takuya Iwamoto, Masahiro Okuda
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2011-10-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝虚血再灌流障害時のCyclosporine Aの経口bioavailability低下における酸化ストレスの役割2011

    • Author(s)
      池村健治、井之上浩一、水谷秀樹、岡尚男、村木優一、岩本卓也、奥田真弘
    • Organizer
      日本薬剤学会第26年会
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2011-10-29
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] マイクロRNA145(miR-145)によるMDR1/P-糖タンパク質(P-gp)の転写後発現調節2012

    • Inventor(s)
      池村健治、岩本卓也、奥田真弘
    • Industrial Property Rights Holder
      国立大学法人三重大学、学校法人金城学院
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-096869
    • Filing Date
      2012-04-20
    • Related Report
      2013 Final Research Report
    • Overseas

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

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