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FUNCTIONAL ANALYSIS OF THE ANIONIC DRUG TRANSPORTERS USING KNOCKOUT MICE

Research Project

Project/Area Number 11670100
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKyorin University

Principal Investigator

INATOMI Jun (2001)  KYORIN UNIVERSITY FACULTY OF MEDICINE FELLOW, 医学部, 助手 (00311960)

車 碩鎬 (1999-2000)  杏林大学, 医学部, 助手 (50276200)

Co-Investigator(Kenkyū-buntansha) TAKEDA Michio  FACULTY OF MEDICINE, KYORIN UNIVERSITY ASSOCIATE PROFESSOR, 医学部, 助教授 (40255401)
KANAI Yoshikatsu  FACULTY OF MEDICINE, KYORIN UNIVERSITY PROFESSOR, 医学部, 教授 (60204533)
ENDOU Hitoshi  FACULTY OF MEDICINE, KYORIN UNIVERSITY PROFESSOR, 医学部, 教授 (20101115)
KIM Do Kyung  FACULTY OF MEDICINE, KYORIN UNIVERSITY FELLOW, 医学部, 助手 (40327474)
HOSOYAMADA Makoto  FACULTY OF MEDICINE, KYORIN UNIVERSITY LECTURER, 医学部, 講師 (00291659)
稲富 淳  杏林大学, 医学部, 助手 (00311960)
関根 孝司  杏林大学, 医学部, 助手 (50255402)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsorganic anion transporter1 / organic anion transporter2 / organic anion transporter3 / knockout mouse / gene targeting / organic anion transporter / drug transporter / pharmacokinetics / kidney / liver / brain
Research Abstract

Living features need the mechanism to excrete their metabolites, drugs, or xenobiotics for their homeostasis. Most of these substances are included in the organic anion, and kidneys or liver have specific pathways to excrete them. Our laboratory cloned organic anion transporter 1 (OAT1), which plays the crutial role in excretion of organic anions in the kidneys. We also cloned OAT2, which is specifically expressed in the liver, or OAT3, which is expressed kidneys, liver, or brain and thoroughly investigated their transport properties. The purpose of this study is to verify the physiological roles of these transporters using the gene targeting.
We prepared cDNA libraries of mouse kidney and liver, and tried the screening of the libraries using the fragments of rat OATs as the probe and finally isolated mouse OAT1, OAT2, and OAT3. We determined their nucleotide sequence, and thoroughly investigated their transport properties using Xenopus oocyte expression system. We also analyzed their tissue distribution by Northern hybridization or immunohistochemistry.
We have prepared the targeting vectors from the genomic information, and have prepared the knock-out mice with the cooperation of the Transgenic. As the knock-out of these clones are not incompatible with life, we are now preparing the in vivo experiment or histopathological analysis of these mice. Thoroughout the in vivo experiments, the data of the in vitro experiments play the significant roles as the fundamental informations.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Takeda Michio: "Human organic anion transporters and human organic cation transportera mcdiatc renal antivirai transport"J Pharmacol Exp Thor. 300(3). 918-924 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Cha Soek Ho: "Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney"Mol Pharmacol. 59(5). 1277-1286 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekine Takashi: "The multispecific organic anion transporter (OAT) family"Pflugers Arch. 440(3). 337-350 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda Michio: "Regulation by protein Kinase C of organic anion transport driven by rat organic anion transporter 3 (rOAT3)"Life Sci. 67(9). 1087-1093 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakajima Noriko: "Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney"Kidney Int. 57(4). 1608-1616 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda, Michio: "Human organic anion transporters and human organic cation transporters mediate renal antiviral transport"J Pharmacol Exp Ther. 300(3). 918-24 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Cha Soek Ho: "Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney"Mol Pharmacol. 59(5). 1277-86 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekine Takashi: "The multispecific organic anion transporter (OAT) family"Pfiugers Arch. 440(3). 337-50 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda Michio: "Regulation by protein kinase C of organic anion transport driven by rat organic anion transporter 3 (rOAT3)"Life Sci. 67(9). 1067-93 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakajima Noriko: "Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney"Kidney Int. 57(4). 1608-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeda Michio: "Human organic anion transporters and human organic cation transporters mediate renal antiviral transport"J Pharmacol Exp Ther. 300(3). 918-924 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cha Soek Ho: "Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney"Mol Pharmacol. 59(5). 1277-1286 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sekine Takashi: "The multispecific organic anion transporter(OAT)family"Pflugers Archi. 440(3). 337-350 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeda Michio: "Regulation by protein kinase C of organic anion transport driven by rat organic anion transporter 3(rOAT3)"Life Sci. 67(9). 1087-1093 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakajima Noriko: "Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney"Kidney Int. 57(4). 1608-1616 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cha SH,Sekine T, et al: "Molecular cloning and characterization of multispecific organic anion transporter 4 expressd in the placenta"J Biol Chem. 275. 4507-12 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakajima N,Sekine T, et al: "Developmental changes in multispecific organic anion transporter 1 (OAT1) expression in the rat kidney."Kidney Int. 57. 1068-16 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuda M,Sekine T, et al: "Transport of ochratoxin A by renal multispecific organic anion transporter 1"J Pharmacol Exp Ther. 289. 1301-5 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sekine T,Cha SH,Endou H: "The multispecific organic anion transporter (OAT) family"Euro J Physiol. 440. 337-50 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wada S,Tsuda M, et al: "Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs."J Pharmacol Exp Ther. 294. 844-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Cha SH,Sekine T, et al: "Identification and characterization of human organic anion transporter 3 expression predominantly in the kidney"Mol Pharmacol. 59(In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Cha SH,Sekine T,et al: "Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta."J Biol Chem. 275. 4507-4512 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakajima N,Sekine T,Cha SH,et al: "Developmental changes in multispecific organic anion transporter 1 (OAT1) expression in the rat kidney."Kidney Int. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sekine T,Cha SH,et al: "Molecular biology of multispecific organic anion transporter family (OAT family).(REVIEW ARTICLE)"Clin Exp Nephrol. 3. 237-243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsada M,Sekine T,et al: "Transport of ochratoxin A by renal multispecific organic anion transporter 1."J Pharmacol Exp Ther. 289. 1301-1305 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Apiwattanakul N,Sekine T,et al: "Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes."Mol Pharmacol. 55. 847-854 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jariyawat S,Sekine T,et al: "The interaction and transport of β-lactam antibiotics with the cloned rat renal organic anion transporter 1 (OAT1)."J. Pharmacol. Exp. Ther.. 290. 672-677 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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