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Clinical implication of organic anion transporters in the proximal tubule

Research Project

Project/Area Number 13671128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKyorin University

Principal Investigator

TAKEDA Michio  Kyorin University School of Medicine Department of Pharmacology, Associate Professor, 医学部, 助教授 (40255401)

Co-Investigator(Kenkyū-buntansha) ENDOU Hitoshi  Kyorin University School of Medicine Department of Pharmacology, Professor, 医学部, 教授 (20101115)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHuman organic anion transporter / Human organic cation transporter / Drug transport / Proximal tubule / Tubular secretion / Clinical implication / stable cell line / ヒト有機カキオントランスポータ / 有機アニオントランスポータ / 有機カチオントランスポータ / 腎排泄
Research Abstract

Human organic anion transporter (hOAT) and human organic cation transporter (hOCT) play important roles in the tubular secretion of drugs. HOAT1, 2, 3, hOCT2 are localized to the basolateral side of the proximal tubule and mediate the uptake of drugs into the proximal tubule. HOAT4 is localized to the apical side of the proximal tubule and mediates the urinary secretion or the reabsorption of drugs. Using cell lines stably expressing these transporters, we have obtained the results as below. 1. Identification of transporters responsible for drug transport: HOATs and hOCTs responsible for renal drug transport were identified as follows; (1) Prostaglandin E2α F2: hOAT1, 2, 3, 4, hOCT1, 2, (2) Antivirals (Acyclovir and Ganciclovir): hOAT1, hOCT1, (3) Antiviral (Zidovudine): hOAT1, 2, 3, 4, (4) Antitumor dug (Methotrexate): hOAT1, 3, 4, (5) Tetracycline: hOAT1, 2, 3, 4, (6) Mycotoxin (Ochratoxin A): hOAT1, 3, 4, (7) Uremic toxin (Indoxyl sulfate): rat-OAT1, OAT3. In (3), it was predicted that the molecule responsible for the drug interaction between methotrexate and nonsteroidal antiinflammatory drugs is hOAT3. 2. Evaluation of organic anion transport inhibitors: We undertook to predict the target hOATs for betamipron and cilastatin, which are co-administered with carbapenpen antibiotics, and probenecid in vivo. It was predicted that betamipron inhibits hOAT1, 3, cilastatin dose hOAT1, and probenecid dose hOAT4 in vivo. 3. Elucidation of OAT in the induction of drug-induced nephrotoxicity: It was suggested that hOAT1, 3 are associated with the induction of odhratoxin A-induced nephrotoxicity, and rOAT1 and rOAT3 are associated with the induction of indoxyl sulfate-induced nephrotoxicity. The current results provide not only the molecular basis for renal drug transport, but also the information for the safer and more efficient use of drugs.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Takeda M et al.: "Characterization of organic anion transport inhibitor using cells stably expressing human organic anion transporters"European Journal of Pharmacology. 419. 113-120 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M et al.: "Human organic anion transporters and organic cation transporters mediate renal antiviral transport"Journal of Pharmacology and Experimental Therapeutics. 300. 918-924 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura H et al.: "Human organic anion transporters and organic cation transporters mediate renal prostaglandin transport"Journal of Pharmacology and Experimental Therapeutics. 301. 293-298 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto A et al.: "Interaction of human organic anion transporter 2 and 4 with organic anion transport inhibitors"Journal of Pharmacology and Experimental Therapeutics. 301. 797-802 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Babu E et al.: "Characterization of ochratoxin A transport by human organic anion transporter 4"Biochimica Biophysica et Acta. 1590. 1711-1720 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M et al.: "Characterization of methotrexate transport and its drug interaction by human organic anion transporters"Journal of Pharmacology and Experimental Therapeutics. 302. 666-671 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 武田 理夫: "Annual Review 腎臓2003 腎での薬物輸送の分子機構とその臨床的意義"中外医学社. 7 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M., Narikawa S., Hosoyamada M., Cha SH., Sekine T., Endou H.: "Characterization of organic anion transport inhibitor using cells stably expressing human organic anion transporters"Eur. J. Pharmacol. 419. 113-120 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jung KY., Takeda M., Kim DK., Tojo A., Narikawa S., Hosoyamada M., Cha SH., Sekine T., Endou H.: "Characterization of ochratoxin A transport by human organic anion transporters"Life Sci. 89. 2123-2135 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M., Khamdang S., Narikawa S., Kimura H., Cha SH., Sekine T., Salthisekaran D., Endou H.: "Human organic anion transporters and organic cation transporters mediate renal antiviral transport"J. Pharmacol. Exp. Ther. 300. 918-924 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jung KY., Takeda M., Shimoda M., Narikawa S., Kim DK., Tojo A., Sekine T., Endou H.: "Role of organic anion transporter 3 (OAT3) in cephaloridine-induced nephrotoxicity"Life Sci. 70. 1-14 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Babu E., Takeda M., Narikawa S., Kobayashi Y., Cha SH., Sekine T., Salthisekaran D., Endou H.: "Characterization of tetracycline transport by human organic anion transporters"Jpn. J. Pharmacol. 88. 69-76 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M., Babu E., Narikawa S., Endou H.: "Interaction of human organic anion transporters with cephalosporin antibiotics"Eur. J. Pharmacol. 438. 137-142 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura H., Takeda M., Narikawa S., Enomoto A., Ichida K., Endou H.: "Human organic anion transporters and organic cation transporters mediate renal prostaglandin transport"J. Pharmacol. Exp. Ther. 301. 293-298 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto A., Takeda M., Narikawa S., Kobayashi Y., Kobayashi Y., Cha SH., Sekine T., Niwa T., Endou H.: "Interaction of human organic anion transporter 2 and 4 with organic anion transport inhibitors"J. Pharmacol. Exp. Ther. 301. 797-802 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto A., Kimura H., Chairoungdua A., Shigeta Y., Jutabha P., Cha SH., Hosoyamada M., Takeda M., Sekine T., Igarashi T., Matsuo H., Kikuchi Y., Oda T., Ichida K., Hosoya T., Shimokata K., Niwa T., Kanai Y., Enodu H.: "Molecular identification of a renal urate/anion exchanger that regulates blood urate levels"Nature. 417. 447-452 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Babu E., Takeda M., Narikawa S., Kobayashi Y., Yamamoto T., Cha SH., Sekine T., Sakthisekaran D., Endou H.: "Characterization of ochratoxin A transport by human organic anion transporter 4"Biochim. Biophys. Acta. 1590. 64-75 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M., Khamdang S., Narikawa S., Kimura H., Cha SH., Sekine T., Endou H.: "Characterization of methotrexate transport and its drug interaction by human organic anion transporters"J. Pharmacol. Exp. Ther. 302. 666-671 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto A., Takeda M., Sekine T., Cha SH., Takayama F., Niwa T., Endou H.: "Role of organic anion transporters in the transport of indoxyl sulfate and the induction of its nephrotoxicity"J. Am. Soc. Nephrol. 13. 1711-1720 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Khamdang S., Takeda M., Narikawa S., Enomoto A., Anzai N., Piyachaturawat P., and Endou H.: "Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflamatory drugs"J. Pharmacol. Exp. Ther. 303. 534-539 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ichida K., Hosoyamada M., Kimura H., Takeda M., Utsunomiya Y., Hosoya T., Endou H.: "Urate transport via the human PAH transporter hOAT1 and its gene structure"Kidney Int. 63. 143-155 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Khandang S., Takeda M., Noshiro R., Enomoto A., Anzai N., Piyachaturawat P., and Endou H.: "Interaction of human organic anion transporter 2 with various cephalosporin antibiotics"Eur. J. Pharmacol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda M et al.: "Characterization of methotrexate transport and its drug interaction by human organic anion transporters"Journal of Pharmacology and Experimental Therapeutics. 302. 666-671 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto A et al.: "Role of organic anion transporters in the transport of indoxyl sulfate and the induction of its nephrotoxicity"Journal of American Society of Nephrology. 13. 1711-1720 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto A et al.: "Molecular identification of a renal urate/anion exchanger that regulates blood urate levels"Nature. 417. 447-452 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto A et al.: "Interactionof human organic anion transporter 2 and 4 with organic anion transport inhibitors"Journal of Pharmacology and Experimental Therapeutics. 301. 797-802 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Khamdang.S et al.: "Interactions of human organic anion transporters and human organic cation trasnporters with nonsteroidal anti-inflamatory drugs"Journal of Pharmacology and Experimental Therapeutics. 303. 534-539 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichida K et al.: "Urate transport via the human PAH transporter hOAT1 and its gene structure"Kidney International. 63. 143-155 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 武田理夫: "Annual Review 腎臓2003腎での薬物輸送の分子機構とその臨床的意義"中外医学社. 7 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda M et al.: "Characterization of organic anion transport inhibitor using cells stably expressing human organic anion transporters"European Journal of Pharmacology. 419. 113-120 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jung KY et al.: "Characterization of ochratoxin A transport by human organic anion transporters"Life Sciences. 89. 2123-2135 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeda M et al.: "Human organic anion transporters and organic cation transporters mediate renal antiviral transport"Journal of Pharmacology and Experimental Therapeutics. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeda M et al.: "Interaction of human organic anion transporters with cephalosporin antibiotics"European Journal of Pharmacology. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Babu E et al.: "Characterization of tetracycline transport by human organic anion transporters"Japanese Journal of Pharmacology. 88. 69-76 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Babu E et al.: "Characterization of ochratoxin A transport by human organic anion transporter 4"Biochimica Biophysics Acta. (印刷中).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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