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Molecular Biological Studies on Relationships between Changes in Renal Tubular Transporter Gene Expressions and Deterioration of Drug Excretory Functions in Renal Diseases

Research Project

Project/Area Number 14370781
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKumamoto University

Principal Investigator

SAITO Hideyuki  Kumamoto University, Hospital Pharmacy, Professor, 医学部附属病院, 教授 (40225727)

Co-Investigator(Kenkyū-buntansha) HAMADA Akinobu  Kumamoto University, Hospital Pharmacy, Lecturer, 医学部附属病院, 講師 (00322313)
MASUDA Satohiro  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90303825)
FUKATSU Atsushi  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90247685)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsDrug transporter / Renal excretion / Renal tubular dysfunction / Nephrotoxicity / Dosage regimen / Renal failure / 尿細管分泌 / 有機アニオン / 有機カチオン / 投与設計 / アニオン性薬物 / カチオン性薬物 / 遺伝子発現
Research Abstract

The proximal tubules of kidney play a pivotal role in limiting or preventing toxicity by secreting organic anions and cations into urine. Organic ion transporter family(SLC22A) appeared to mediate renal secretion of these molecules. Organic anion transporters, OAT-K1 and OAT-K2 could serve as multispecific transporters, mediating transport of a wide variety of endogenous substances and xenobiotics. The levels of urinary excretion of dmetidine was reduced under cronic renal failure(CRF) partiy due to the reduced expression of rOCT2, and the lowered plasma level of testosterone was suggested to be responsible for the depressed rOCT2 expression in CRF. hOAT3 was suggested to play an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (33 results)

All 2005 2004 2003 2002 Other

All Journal Article (20 results) Publications (13 results)

  • [Journal Article] Pharmacokinetic changes of Irinotecan by intestinal alkalization in advanced colorectal cancer patient.2005

    • Author(s)
      Hamada A.
    • Journal Title

      Therap.Drug Monit. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Methotrexate-loxoprofen interaction : involvement of human organic anion transporters hOAT1 and hOAT3.2004

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

      Drug Metab.Pharmacokinet. 19・5

      Pages: 369-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats.2004

    • Author(s)
      Yamaguchi, H., et al.
    • Journal Title

      Pharm.Res. 21・2

      Pages: 330-338

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Decreased expression of glucose and peptide transporters in rat remnant kidney.2004

    • Author(s)
      Nakamura, N., et al.
    • Journal Title

      Drug Metabol.Pharmacokin. 19・1

      Pages: 41-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Gene expression variance based on random sequencing in rat remnant kidney.2004

    • Author(s)
      Horiba, N., et al.
    • Journal Title

      Kidney Int. 66・1

      Pages: 29-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases.2004

    • Author(s)
      Sakurai, Y., et al.
    • Journal Title

      Pharm.Res. 21・1

      Pages: 61-67

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Common single nucleotide polymorphisms of the MDR1 gene have no influence on its mRNA expression level of normal kidney cortex and renal cell carcinoma in Japanese nephrectomized patients.2004

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

      J.Hum.Genet. 49・1

      Pages: 40-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Methotrexate-loxoprofen interaction : involvement of human organic anion transporters hOAT1 and hOAT3.2004

    • Author(s)
      Uwai, Y.
    • Journal Title

      Drug Metab.Pharmacokinet. 19(5)

      Pages: 369-374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats.2004

    • Author(s)
      Yamaguchi, H.
    • Journal Title

      Pharm.Res. 21(2)

      Pages: 330-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased expression of glucose and peptide transporters in rat remnant kidney.2004

    • Author(s)
      Nakamura, N.
    • Journal Title

      Drug Metab.Pharmacokinet. 19(1)

      Pages: 41-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression variance based on random sequencing in rat remnant kidney.2004

    • Author(s)
      Horiba, N.
    • Journal Title

      Kidney Int. 66(1)

      Pages: 29-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression levels of renal organic anion transporters(OATs) and their correlation with anionic drug excretion in patients with renal diseases.2004

    • Author(s)
      Sakurai, Y.
    • Journal Title

      Pharm.Res. 21(1)

      Pages: 61-67

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Common single nucleotide polymorphisms of the MDR1 gene have no influence on its mRNA expression level of normal kidney cortex and renal cell carcinoma in Japanese nephrectomized patients.2004

    • Author(s)
      Uwai, Y.
    • Journal Title

      J.Hum.Genet. 49(1)

      Pages: 40-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression variance based on random sequencing in rat remnant kidney.2004

    • Author(s)
      Horiba.N., et al.
    • Journal Title

      Kidney Int. 66・1

      Pages: 29-45

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased activity of base-lateral organic ion transports in hyperuricemic rat kidney : roles of organic ion transporters, rOAT1, rOAT3 and rOCT2.2003

    • Author(s)
      Habu, Y.
    • Journal Title

      Biochem Pharmacol. 66(6)

      Pages: 1107-1114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Decreased expression of P-glycoprotein during differentiation in the human intestinal cell line Caco-2.2003

    • Author(s)
      Goto, M.
    • Journal Title

      Biochem Pharmacol. 66(1)

      Pages: 163-170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distinct transport activity of tetraethylammonium from L-carnitine in rat renal brush-border membranes.2003

    • Author(s)
      Ohnishi, S.
    • Journal Title

      Biochim.Biophys.Acta 1609(2)

      Pages: 218-224

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction of imatinib mesilate with human P-glycoprotein.2003

    • Author(s)
      Hamada, A.
    • Journal Title

      J.Pharmacol.Exp.Ther. 307(2)

      Pages: 824-828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] p-Aminohippurate transport at the apical membrane in the OK kidney epithelial cell line.2002

    • Author(s)
      Habu, Y.
    • Journal Title

      Pharm.Res. 19(12)

      Pages: 1822-1826

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Down-regulation of rat organic cation transporter rOCT2 by 5/6 nephrectomy.2002

    • Author(s)
      Ji, L.
    • Journal Title

      Kidney Int. 62(2)

      Pages: 514-524

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Sakurai, Y., et al.: "Expression levels of renal organic anion transporters (OATS) and their correlation with anionic drug excretion in patients with renal diseases."Pharm.Res.. 21・1. 61-67 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Uwai, Y., et al.: "Common single nucleotide polymorphisms of the MDR1 gene have no influence on its mRNA expression level of normal kidney cortex and renal cell carcinoma in Japanese nephrectomized patients"J.Hum.Genet.. 49・1. 40-45 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Igarashi, T., et al.: "Decreased cyclosporin A concentrations in the absorption phase using microemulsion preconcentrate formulation in rats with cisplatin-induced acute renal failure."Biol.Pharm.Bull.. 26・11. 1591-1595 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Habu, Y., et al.: "Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney : roles of organic ion transporters, rOAT1, rOAT3 and rOCT2."Biochem.Pharmacol.. 66・1. 163-170 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamada, A., et al.: "Interaction of imatinib mesilate with human P-glycoprotein."J.Pharmacol.Exp.Ther.. 307・2. 824-828 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohnishi, S., et al.: "Distinct transport activity of tetraethylammonium from L-carnitine in rat renal brush-border membranes."Biochim.Biophys.Acta. 1609・2. 218-224 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小川久雄, 等: "慢性心不全のマネジメント-新たな展開-"医薬ジャーナル社. 143 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okabe, H., et al.: "Evaluation of increased bioavailability of tacrolimus in rats with experimental renal dysfunction"J.Pharm.Pharmacol.. 54・1. 65-70 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Motohashi, H., et al.: "Gene expression levels and immunolocalization of organic ion transporters in the human kidney"J.Am.Soc.Nephrol.. 13・4. 866-874 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Urakami, Y., et al.: "cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney"J.Am.Soc.Nephrol.. 13・7. 1703-1710 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ji, L., et al.: "Down-regulation of rat organic cation transporter rOOT2 by 5/6 nephrectomy"Kidney Int.. 62・2. 514-524 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Habu, Y., et al.: "P-aminohippurate transport at the apical membrane in the OK kidney epithelial cell line"Pharm.Res.. 19・12. 1822-1826 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Onishi, S., et al.: "Distinct transport activity of tetraethylammonium from L-carnitine in rat renal brush-border membranes"Biochim.Biophys.Acta. 1609・2. 218-224 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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