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Development of novel anti-uricosuric agents based on the genomic strategy.

Research Project

Project/Area Number 14207004
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

ENDOU Hitoshi  Kyorin University, Professors emeritus, 名誉教授 (20101115)

Co-Investigator(Kenkyū-buntansha) KANAI Yoshikatsu  Kyorin University, School of Medicine, Professor, 医学部, 教授 (60204533)
HOSOYAMADA Makoto  Kyorin University, School of Medicine, Lecturer, 医学部, 講師 (00291659)
ANZAI Naohiko  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (70276054)
IRIBE Yuji  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (20348618)
HIRATA Taku  Kyorin University, School of Medicine, Assistant, 医学部, 助手 (60372918)
横山 宏和  杏林大学, 医学部, 助手
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥39,910,000 (Direct Cost: ¥30,700,000、Indirect Cost: ¥9,210,000)
Fiscal Year 2004: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2003: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2002: ¥21,190,000 (Direct Cost: ¥16,300,000、Indirect Cost: ¥4,890,000)
KeywordsFamilial renal hypouricemia / Hyperuricemia / URAT1 / PDZK1 / Organic anion transporter / renal stones / genetic factor / gout / 近位尿細管性アシドーシス / シスチン尿症 / BAT1 / rBAT / ナトリウム / 重炭酸イオン共輸送体 / 環境因子 / ゲノム / 尿酸トランスポーター / 尿酸 / 特発性低尿酸血症 / イーストツーハイブリド法 / PDZK 1 / ベンズプロマロン / ベンズブロマロン
Research Abstract

Urate is the major inert end product of purine degradation in higher primates in contrast to most other mammals because of the genetic silencing of hepatic oxidative enzyme uricase. The kidney plays a dominant role in urate elimination ; it excretes 70% of the daily urate production. Therefore, it is important to understand renal urate handling mechanism because the underexcretion of urate has been implicated in the development of hyperuricemia that leads to gout. The urate transport systems exist in the proximal tubule but they are complicated because of their bidirectional transport and the species differences. Recently, we have identified the urate-anion exchanger URAT1 (SLC22A12) in the human kidney and found that defects in SLC22A12 lead to idiopathic renal hypouricemia. URAT1 is targeted by uricosuric and antiuricosuric agents that affect urate excretion. Molecular identification of urate transporting proteins will lead to the new drug development for hyperuricemia.
We also found … More that defects in SLC22A12 lead to idiopathic renal hypouricaemia (MIM number, 220150) and patients with such defects show a high fractional urate excretion such as 95 ± 10 % (normally <10%). These results indicate that URAT1 regulates blood urate level and vice versa, that is, to control blood urate levels, the URAT1 transport function should be regulated. A newly found genetic alteration in SLC22A12 from a patient of an idiopathic renal hypouricaemia has prompted us to consider the importance of the URAT1 extreme intracellular C-terminal region for its function. A 5-bp deletion near the URAT1 C-terminal end (1639-1643del) causes frameshift and the seven amino acids in the terminal sequences have changed into eight different amino acids. The URAT1 transport activity of this mutation is low in the Xenopus oocyte expression system. Interestingly, the PDZ binding motif at the C-terminal end of URAT1, which is known to participate in protein-protein interaction, disappears by this amino acid sequence modification.
In this study, we use the yeast two-hybrid approach to investigate the putative URAT1-associated proteins that modulate its transport function. We identify the multivalent PDZ domain-containing protein PDZK1 as an apparent partner of URAT1 in the human kidney. Moreover, we show a functional consequence of PDZK1/URAT1 interaction in transfected HEK293 cells, where URAT1 transport activities were increased by 1.4-fold by coexpression of PDZK1. We speculate that PDZK1 is a scaffolding protein that may be a physiological regulator of the function of URAT1. Less

Report

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

    (112 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (77 results) Book (4 results) Patent(Industrial Property Rights) (3 results) Publications (28 results)

  • [Journal Article] Dual-color imaging of nuclear-cytoplasmic dynamics, viability, and proliferation of cancer cells in the portal vein area2006

    • Author(s)
      Tsuji K
    • Journal Title

      66(1)

      Pages: 303-306

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter2006

    • Author(s)
      Shigeta Y
    • Journal Title

      69(7) 2006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dual-color imaging of nuclear-cytoplasmic dynamics, viability, and proliferation of cancer cells in the portal vein area.2006

    • Author(s)
      Tsuji K, Yamauchi K, Yang M, Jiang P, Bouvet M, Endo H, Kanai Y, Yamashita K, Moossa AR, Hoffman RM.
    • Journal Title

      Cancer Res. 66(1)

      Pages: 303-306

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter.2006

    • Author(s)
      Shigeta Y, Kanai Y, Chairoungdua A, Ahmed N, Sakamoto S, Matsuo H, Kim DK, Fujimura M, Anzai N, Mizoguchi K, Ueda T, Akakura K, Ichikawa T, Ito H, Endou H.
    • Journal Title

      Kidney Int. 69(7)

      Pages: 1198-1206

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular physiology of renal organic anion transporters.2006

    • Author(s)
      Sekine T, Miyazaki H, Endou H.
    • Journal Title

      Am J Physiol Renal Physiol. 290(2)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia2005

    • Author(s)
      Wakida N
    • Journal Title

      J Clin Endocrinol Metab 90(4)

      Pages: 2169-2174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional characterization of rat organic anion transporter 5 (Slc22a19) at the apical membrane of renal proximal tubules2005

    • Author(s)
      Anzai N
    • Journal Title

      J Pharmacol Exp Ther 315(2)

      Pages: 534-544

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Modulation of renal apical organic anion transporter 4 function by two PDZ domain-containing proteins2005

    • Author(s)
      Miyazaki H
    • Journal Title

      J Am Soc Nephrol 16(129

      Pages: 3498-3506

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Altered expression of rat renal cortical OAT1 and OAT3 in response to bilateral ureteral obstruction2005

    • Author(s)
      Villar SR
    • Journal Title

      Kidney Int 68(6)

      Pages: 2704-2713

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular physiology of urate transport2005

    • Author(s)
      Hediger MA
    • Journal Title

      Physiology (Bethesda) 20

      Pages: 125-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Integrated physiology of proximal tubular organic anion transport2005

    • Author(s)
      Anzai N
    • Journal Title

      Curr Opin Nephrol Hypertens 14(5)

      Pages: 472-479

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia.2005

    • Author(s)
      Wakida N, Tuyen do G, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K.
    • Journal Title

      J Clin Endocrinol Metab. 90(4)

      Pages: 2169-2174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional characterization of rat organic anion transporter 5 (Slc22a19) at the apical membrane of renal proximal tubules.2005

    • Author(s)
      Anzai N, Jutabha P, Enomoto A, Yokoyama H, Nonoguchi H, Hirata T, Shiraya K, He X, Cha SH, Takeda M, Miyazaki H, Sakata T, Tomita K, Igarashi T, Kanai Y, Endou H.
    • Journal Title

      J Pharmacol Exp Ther. 315(2)

      Pages: 534-544

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Modulation of renal apical organic anion transporter 4 function by two PDZ domain-containing proteins.2005

    • Author(s)
      Miyazaki H, Anzai N, Ekaratanawong S, Sakata T, Shin HJ, Jutabha P, Hirata T, He X, Nonoguchi H, Tomita K, Kanai Y, Endou H.
    • Journal Title

      J Am Soc Nephrol. 16(12)

      Pages: 3498-3506

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Altered expression of rat renal cortical OAT1 and OAT3 in response to bilateral ureteral obstruction.2005

    • Author(s)
      Villar SR, Brandoni A, Anzai N, Endou H, Torres AM.
    • Journal Title

      Kidney Int. 68(6)

      Pages: 2704-2713

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular physiology of urate transport.2005

    • Author(s)
      Hediger MA, Johnson RJ, Miyazaki H, Endou H.
    • Journal Title

      Physiology (Bethesda). 20

      Pages: 125-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Integrated physiology of proximal tubular organic anion transport.2005

    • Author(s)
      Anzai N, Jutabha P, Kanai Y, Endou H.
    • Journal Title

      Curr Opin Nephrol Hypertens. 14(5)

      Pages: 472-479

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Neprhrin and podocin expression aroung the onset of puromycin aminonucleoside nephrosis.2005

    • Author(s)
      Hosoyamada M, Yan K, Nishibori Y, Takiue Y, Kudo A, Kawkami H, Shibasaki T, Endou H
    • Journal Title

      J.Pharmacol.Sci. 97

      Pages: 234-241

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interactions of human organic anion transporters with diuretics2004

    • Author(s)
      Hasannehad H
    • Journal Title

      J Pharmacol Exp Ther 308(3)

      Pages: 1021-1029

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC2A1) affecting transport functions2004

    • Author(s)
      Sakata T
    • Journal Title

      Biochem Biophys Res Commun 313(3)

      Pages: 789-793

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Function and localization of urate transporter 1 in mouse kidney2004

    • Author(s)
      Hosoyamada M
    • Journal Title

      J Am Soc Nephrol 15(2)

      Pages: 261-268

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition2004

    • Author(s)
      Ljubojevic M
    • Journal Title

      Am J Phyciol Renal Physiol 287(1)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The multivalent PDZ -containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus2004

    • Author(s)
      Anzai N
    • Journal Title

      J BIol CHem 279(44)

      Pages: 45942-45950

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The multispecific organic anion transporter family : properties and pharmacological significance2004

    • Author(s)
      Miyazaki H
    • Journal Title

      Trends Pharmacol Sci 25(12)

      Pages: 654-662

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets2004

    • Author(s)
      Takahashi R
    • Journal Title

      290(2) 2006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interactions of human organic anion transporters with diuretics.2004

    • Author(s)
      Hasannejad H, Takeda M, Taki K, Shin HJ, Babu E, Jutabha P, Khamdang S, Aleboyeh M, Onozato ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H.
    • Journal Title

      J Pharmacol Exp Ther. 308(3)

      Pages: 1021-1029

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions.2004

    • Author(s)
      Sakata T, Anzai N, Shin HJ, Noshiro R, Hirata T, Yokoyama H, Kanai Y, Endou H.
    • Journal Title

      Biochem Biophys Res Commun. 313(3)

      Pages: 789-793

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Function and localization of urate transporter 1 in mouse kidney.2004

    • Author(s)
      Hosoyamada M, Ichida K, Enomoto A, Hosoya T, Endou H.
    • Journal Title

      J Am Soc Nephrol. 15(2)

      Pages: 261-268

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rat renal cortical OAT1 and OAT3 exhibit gender differences determined by both androgen stimulation and estrogen inhibition.2004

    • Author(s)
      Ljubojevic M, Herak-Kramberger CM, Hagos Y, Bahn A, Endou H, Burckhardt G, Sabolic I.
    • Journal Title

      Am J Physiol Renal Physiol. 287(1)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The multivalent PDZ-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.2004

    • Author(s)
      Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H.
    • Journal Title

      J Biol Chem. 279(44)

      Pages: 45942-45950

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The multispecific organic anion transporter family : properties and pharmacological significance.2004

    • Author(s)
      Miyazaki H, Sekine T, Endou H.
    • Journal Title

      Trends Pharmacol Sci. 25(12)

      Pages: 654-662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evidence for a role of human organic anion transporters in the muscular side effects of HMG-GoA reductase inhibitors.2004

    • Author(s)
      Takeda M, Norshio R, Onozato ML, Tojo A, Hasannejad H, Hang XL, Narikawa S, Endou H.
    • Journal Title

      Eur.J.Phamacol. 483

      Pages: 133-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Novel single nucleotide polymorphisms of organic cation transporter 1(SLC22A1) affecting transport functions.2004

    • Author(s)
      Sakata T, Anzai N, Shin HJ, Norhiro R, Hirata T, Yokoyama H, Kanai Y, Endou H.
    • Journal Title

      Biochem Biophys Res comm. 313

      Pages: 789-793

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interactions of human organic anion transporters with diuretics.2004

    • Author(s)
      Hasannejad H, Takeda M, Taki K, Jung SH, Babu E, Jutabha P, Khamdang S, Aleboyen M, Onodera ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H.
    • Journal Title

      J Pharmacol Exp Ther 308(3)

      Pages: 1021-1029

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interactions of human- and rat-organic anion transporters with pravastatih and cimetidine.2004

    • Author(s)
      Khamdan S, Takeda M, Shimoda M, Noshiro Ri, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Hitoshi E
    • Journal Title

      Pharmacol Sci. 94

      Pages: 197-202

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CATs and HATs : the SLC7 family of amino acid transporters.2004

    • Author(s)
      Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y.
    • Journal Title

      Pflugers Arch. 447

      Pages: 532-542

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human organic anion transporter 4 is a renal apical organis anion / dicarboxylate exchanger in the proximal tubules.2004

    • Author(s)
      Ekaratanawong S, Anzai N, Jutabha P, Miyazaki H, Noshiro R, Takeda M, Kanai, Endou H.
    • Journal Title

      Pharmacol Sci 94

      Pages: 297-304

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells.2004

    • Author(s)
      Yoon JH, Kim YB, Kim MS, Park JC, Cook JK, Kook KK, Jung HM, Kim SG, Yoo H, Ko YM, Lee SH, Kim BY, Chun HS, Kanai Y, Endou H, Kim DK
    • Journal Title

      Cancer Lett. 205

      Pages: 215-226

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Preferential expression of L-type amino acid transporter 1 in ameloblasts during rat tooth development.2004

    • Author(s)
      Park JC, Kim YB, Yoon H, Kim HJ, Kim SN, Kanai Y, Endou H, Kim DK
    • Journal Title

      Anat Histol Embryol 33

      Pages: 119-124

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The genetic polymorphism of drub transporters : functional analysis approaches.2004

    • Author(s)
      Ishikawa T, Tsuji A, Inui K, Sai Y, Anzai N, Wada M, Endou H, Sumino Y
    • Journal Title

      Phamacogeneomics 5(1)

      Pages: 67-99

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mutation and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis.2004

    • Author(s)
      Inatomi J, Horita S, Braverman N, Sekine T, Yamada H, Suzuki Y, Kawahara K, Moriyama N, Kudo A, Kawakami H, Shimadzu M, Endou H, Fujita T, Seki G, Igarashi T
    • Journal Title

      Pfluegers Arch-Eur.J.Physiol. 448

      Pages: 438-444

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.2004

    • Author(s)
      Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T
    • Journal Title

      J Am Soc Neprol 15

      Pages: 164-173

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese.2004

    • Author(s)
      Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H.
    • Journal Title

      Kidney Int. 66

      Pages: 935-944

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The SLC22 drug transporter family.2004

    • Author(s)
      Koepsell H, Endou H.
    • Journal Title

      Pflugers Arch. 44

      Pages: 666-676

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human organic cation transporter 3 mediates the transport of antiarrhythmic drugs.2004

    • Author(s)
      Hassannejad H, Takeda M, Narikawa S, Huang XL, Enomoto A, Taki K, Niwa T, Shin HJ, Onozato ML, Tojo A, Endou H
    • Journal Title

      Euro J Pharmacol. 499

      Pages: 45-51

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.2004

    • Author(s)
      Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H
    • Journal Title

      J Biol Chem 279(44)

      Pages: 45942-45950

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The multispecific organic anion transporter family : properties and pharmacological significance.2004

    • Author(s)
      Miyazaki H, Sekine T, Endou H
    • Journal Title

      Trends Pharmacol Sci. 25(12)

      Pages: 654-662

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 尿酸トランスポーターの分子実体2004

    • Author(s)
      細山田 真, 金井 好克, 遠藤 仁
    • Journal Title

      Gout and Nucleic Acid Metabolism 28(1)

      Pages: 1-5

    • NAID

      10014068515

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Disease-causing missense mutations in NPHS2 gene alter normal nephrin trafficking to the plasma membrane.2004

    • Author(s)
      Nishibori Y, Liu L, Hosoyamada M, Endou H, Kudo A, Takenaka H, Higashihara E, Bessho F, Takahashi S, Kershaw D, Ruotsalainen V, Tryggvason K, Khoshnoodi J, Yan K
    • Journal Title

      Kidney Int. 66

      Pages: 1755-1765

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Qunatitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drug in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier.2004

    • Author(s)
      Nozaki Y, Kusuhara H, Endou H, Sugiyama Y
    • Journal Title

      J Pharmacol Exp Ther. 309(1)

      Pages: 226-234

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of rat organic anion transporter 3 in the uptake of an organic herbicide, 2,4-dichlorophenoxycetate, by the isolated rat choroids plexus.2004

    • Author(s)
      Nagata Y, Kusuhara H, Imaoka T, Endou H., Sugiyama Y
    • Journal Title

      J Pharm Sci 93(1)

      Pages: 2724-2732

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-coA reductase inhibitors across the blood-brain barrier.2004

    • Author(s)
      Kikuchi R, Kusuara H, Abe T, Endou H, Sugiyama Y.
    • Journal Title

      J Pharmacol Exp Ther 311(3)

      Pages: 1147-1153

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Carrier-mediated uptake of H2-receptor antagonists by the rat choroids plexus : involvement of rat organic anion transporter 3.2004

    • Author(s)
      Nagata Y, Kusuhara H, Hirono S, Endou H, Sugiyama Y
    • Journal Title

      Drug Metab.Dispos. 32

      Pages: 1040-1047

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Urate transport via human PAH transporter h0AT1 and its gene structure2003

    • Author(s)
      Ichida K
    • Journal Title

      Kidney Int 63(1)

      Pages: 143-155

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics2003

    • Author(s)
      Khamdang S
    • Journal Title

      Eur J Pharmacol 465(1-2)

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction of human organic anion as well as cation transporters with indoxyl sulfate2003

    • Author(s)
      Enomoto A
    • Journal Title

      Eur J Pharmacol 466(1)

      Pages: 13-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule.2003

    • Author(s)
      Jutabha P
    • Journal Title

      J Biol Chem 278(30)

      Pages: 27930-27938

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters2003

    • Author(s)
      Babu E
    • Journal Title

      J Biol Chem 278(44)

      Pages: 43838-43835

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity2003

    • Author(s)
      Kanai Y
    • Journal Title

      J Toxicol Sci 28(1)

      Pages: 1-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Urate transport via human PAH transporter hOAT1 and its gene structure.2003

    • Author(s)
      Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, Endou H.
    • Journal Title

      Kidney Int. 63(1)

      Pages: 143-155

    • 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 human and rat organic anion transporter 2 with various cephalosporin antibiotics.2003

    • Author(s)
      Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H.
    • Journal Title

      Eur J Pharmacol. 465(1-2)

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interactions of human organic anion as well as cation transporters with indoxyl sulfate.2003

    • Author(s)
      Enomoto A, Takeda M, Taki K, Takayama F, Noshiro R, Niwa T, Endou H.
    • Journal Title

      Eur J Pharmacol. 466(1-2)

      Pages: 13-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule.2003

    • Author(s)
      Jutabha P, Kanai Y, Hosoyamada M, Chairoungdua A, Kim do K, Iribe Y, Babu E, Kim JY, Anzai N, Chatsudthipong V, Endou H.
    • Journal Title

      J Biol Chem. 278(30)

      Pages: 27930-27938

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters.2003

    • Author(s)
      Babu E, Kanai Y, Chairoungdua A, Kim do K, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmed N, Sakamoto S, Anzai N, Nagamori S, Endou H.
    • Journal Title

      J Biol Chem. 278(44)

      Pages: 43838-43845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity.2003

    • Author(s)
      Kanai Y, Endou H.
    • Journal Title

      J Toxicol Sci. 28(1)

      Pages: 1-17

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The human T-type amino acid trasporter-1; Characterization, gene organization, and chromosomal location2002

    • Author(s)
      Kim DK
    • Journal Title

      Genomics 79

      Pages: 95-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transport of amino acid-related compounds mediated by L-type amino acid transorter 1 (LAT1) : Insights into the mechanisms of substrate recognition2002

    • Author(s)
      Uchino H
    • Journal Title

      Mol Pharmacol 61

      Pages: 729-737

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel Na^<+->independent acidic amino acid transporter with structural similarity to the member of heterodimeric amino acid transporter family associated with unknown heavy chains2002

    • Author(s)
      Matsuo H
    • Journal Title

      J Biol Chem 277

      Pages: 21017-21026

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3 in rat kidney2002

    • Author(s)
      Kojima R
    • Journal Title

      J Am Soc Nephrol 13

      Pages: 848-857

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular identification of a renal urate-anion exchanger that regulates blood urate levels2002

    • Author(s)
      Enomoto A
    • Journal Title

      Nature 417

      Pages: 447-452

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular identication of a novel carnitine transporter specific of human testis2002

    • Author(s)
      Enomoto A
    • Journal Title

      J Biol Chem 277

      Pages: 36262-26271

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The human T-type amino acid transporter-1 ; Characterization, gene organization, and chromosomal location.2002

    • Author(s)
      Kim DK, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H.
    • Journal Title

      Genomics 79

      Pages: 95-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transport of amino acid-related compounds mediated by L-type amino acid transorter 1 (LAT1) : Insights into the mechanisms of substrate recognition.2002

    • Author(s)
      Uchino H, Kanai Y, Kim DK, Wenpe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H.
    • Journal Title

      Mol Pharmacol. 61

      Pages: 729-737

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel Na+-independent acidic amino acid transporter with structural similarity to the member of heterodimeric amino acid transporter family associated with unknown heavy chains.2002

    • Author(s)
      Matsuo H, Kanai Y, Kim JY, Chairungdua A, Kim DK, Inatomi J, Shigeta, Y, Ishimine H, Chekuntode S, Tachampa K, Choi HW, Babu E, Fukuda J, Endou H.
    • Journal Title

      J Biol Chem. 277

      Pages: 21017-21026

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Immunolocalization of multispecific organic anion transporters, OAT1, OAT2 and OAT3 in rat kidney.2002

    • Author(s)
      Kojima R, Sekine T, Kawachi M, Cha S.M., Suzuki Y, Endou H.
    • Journal Title

      J Am Soc Nephrol. 13

      Pages: 848-857

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular identification of a renal urate-anion exchanger that regulates blood urate levels.2002

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

      Nature 417

      Pages: 447-452

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular identication of a novel carnitine transporter specific of human testis.2002

    • Author(s)
      Enomoto A, Wempe MF, Tsuchida H, Shin HJ, Cha SH, Anzai N, Goto A, Sakamoto A, niwa T, Kanai Y, Anders MW, Endou H.
    • Journal Title

      J Biol Chem 277

      Pages: 36262-26271

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review腎臓20052005

    • Author(s)
      宮崎 博喜
    • Total Pages
      6
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review腎臓20042004

    • Author(s)
      安西 尚彦
    • Total Pages
      6
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Annual Review腎臓20032003

    • Author(s)
      榎本 篤
    • Total Pages
      4
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] シリーズ・バイオサイエンスの新世紀2002

    • Author(s)
      金井好克
    • Total Pages
      8
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 硫酸抱合体を選択的に輸送するトランスポーター及びその遺伝子

    • Inventor(s)
      遠藤 仁
    • Industrial Property Rights Holder
      遠藤 仁
    • Industrial Property Number
      2002-070985
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 血管障害や高血圧症の治療・予防剤、及びそのスクリーニング法

    • Inventor(s)
      遠藤 仁
    • Industrial Property Rights Holder
      遠藤 仁
    • Industrial Property Number
      2003-384863
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 中性アミノ酸とランスポーターによる癌の検出法及びそのためのキット

    • Inventor(s)
      遠藤 仁
    • Industrial Property Rights Holder
      遠藤 仁
    • Industrial Property Number
      2004-076282
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Enomoto, A., Kimura, H., Chairoungdua, Okubo, M., Yamada, K., Hosoyamada, M., Shibasaki, T., Endou, H.: "Cadmium transport by human Nramp 2 expressed in Xenopus laevis oocytes."Toxicol.Applied Pharmacol.. 187. 162-167 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Enomoto, A., Takeda, M., Taki, K., Takayama, F., Noshiro, R., Niwa, T., Endou, H.: "Interactions of human organic anion as well as carion transporters with indoxyl sulfate."Euro.J.Pharmacol.. 466. 13-20 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Satoh, H., Moriyama, N., Hara, C., Yamada, H., Horita, S., Kunimi, M., Tsukamoto, K., Iso-o, N., Inatomi, J., Kawakami, H., Kudo, A., Endou, H., Igarashi, T., Goto, A., Fujita T, Seki G: "Localization of Na^+-HCO_3^- cotransporter (NBC-1) variants in rat and human pancreas."Am.J.Physiol.Cell Physiol.. 284. C729-C737 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanai, Y., Endou, H.: "Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity."J.Toxicol.Sci.. 28. 1-17 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hasegawa, M., Kusuhara, H., Endou, H., Sugiyama, Y.: "Contribution of organic anion transporters to the renal uptake of anionic compounds and nucleoside derivatives in rat."J.Pharmacol.Exp.Ther.. 305(3). 1087-1097 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jutabha, P., Kanai, Y., Hosoyamada, M., Chairoungdua, A., Kim, D.K., Iribe, Y., Babu, E., Kim, J.Y., Anzai, N., Chatsudthipong, V., Endou, H.: "Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule."J.Biol.Chem.. 278(30). 28930-27938 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hosoya K, Tomi M, Ohtsuki S, Takanaga H, Saeki S, Kanai Y, Endou H, Naito M, Tsuruo T, Terasaki T: "Enhancement of L-cystine transport activity and its relation to xCT gene induction at the blood-brain barrier by diethyl maleate treatment."J Pharmacol Exp Ther.. 302(1). 225-231 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka M, Itoh K, Matsushita K, Matsushita K, Wakita N, Adachi M, Nonoguchi H, Kitamura K, Hosoyamada M, Endou H, Tomita K.: "Two male siblings with hereditary renal hypouricemia and exercise-induced ARF."Am J Kidney Dis.. 42(6). 1287-1292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Babu E, kanai Y, Chairoungdua A, Kim do K, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmed N, Sakamoto S, Anzai N, Nagamori S, Endou H.: "Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters."J Biol Chem.. 278(44). 43838-43845 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim GH, Na KY, Kim SY, Joo KW, Oh YK, Chae SW, Endou H, Han JS.: "Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney."Nephrol Dial Transplant.. 18(8). 1505-1511 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Alebouyeh M, Takeda M, Onozato ML, Tojo A, Noshiro R, Hasannejad H, Inotaomi J, Narikaw S, Huang XL, Khamdang, Anzai N, Endou H: "Expression of human organic anion transorters in the choroid plexus and their interactions with neurotransmitter metabolites."J Pharmachol sci.. 93. 430-436 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoon JH, Kim YB, Kanai Y, Endou H, Kim DK: "Sequential Increases in 4F2hc expression during DMBA-induced hamster buccal pouch cacinogenesis."Anticancer Res.. 23. 3877-3882 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka M., Itoh K., Matsushita K, Matsushita K, Wakita N, Adachi M, Nonoguchi H, Kitamura K, Hosoyamada M, Endou H, Tomita K.: "Two male siblings with hereditary renal hypouricemia and exercise-induced ARF."Am.J.Kidney Des.. 42(6). 1287-1292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takeda M, Norshio R, Onozato ML, Tojo A, Hasannejad H, Hang XL, Narikawa S, Endou H.: "Evidence for a role of human organic anion transporters in the muscular side effects of HMG-GoA reductase inhibitors."Eur.J.Pharmacol.. 483. 133-138 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakata T, Anzai N, Shin HJ, Norhiro R, Hirata T, Yokoyama H, Kanai Y, Endou H.: "Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions."Biochem Biophys Res Comm.. 313. 789-793 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hasannejad H, Takeda M, Taki K, Jung SH, Babu E, Jutabha P, Khamdang S, Aleboyeh M, Onodera ML, Tojo A, Enomoto A, Anzai N, Narikawa S, Huang XL, Niwa T, Endou H.: "Interactions of human organic anion transporters with diuretics."J Pharmacol Exp Ther.. 308(3). 1021-1029 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Khamdan S, Takeda M, Shimoda M, Noshiro Ri, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Hitoshi E: "Interactions of human- and rat-organic anion transporters with pravastatih and cimetidine."J Pharmachol sci.. 94. 197-202 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ekaratanawong S, Anzai N, Jutabha P, Miyazaki H, Noshiro R, Takeda M, Kanai Y, Sophasan S, Endou H: "Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules."Biochem Biophys Res Comm.. 94. 297-304 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y.: "CATs and HATs : the SLC7 family of amino acid transporters."Pflugers Arch.. 447. 532-542 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koepsell H, Endou H.: "The SLC22 drug transporter family."Pflugers Arch.. 447. 666-676 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 安西尚彦, 宮崎博喜, 遠藤 仁: "細胞内結合タンパク質による膜輸送体機能制御Annual Review 腎臓2004、伊藤克己等編"中外医学社. 6 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Enomoto, A., Kimura, H., Chairoungdua, A., Shigeta, Y., Jutabha, P., Cha, S.H., Hosoyamada, M., Takeda, M., Sekine, T., Igarashi, T., Matsuo, H., Kikuchi, Y., Oda, T., Ichida, K., Hosoya, T., Shimokata, K., Niwa, T., Kanai Y., Endou, H: "Molecular identification of a renal urate-anion exchanger that regulates blood urate leveis"Nature. 417(6887). 447-452 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda M., Khamdang S., Narikawa S., Kimura H., Hosoyamada M., Cha SH., Sekine T., Endou H: "Characterization of methotrexate transport and its drug interactions with human organic anion transporters"J.Pharmacol.Exp.Ther. 302(2). 666-671 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto A., Takeda M., Tojo A., Sekine T., Cha SH., Khamdang S., Takayama E., Aoyama I., Nakamura S., Endou H., Niwa T: "Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxixity"J.Am.Soc.Nephrol.. 13. 1711-1720 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Enomoto A, Michael F, Wempe, Tsuchida H, Shin HJ, Cha SH, Anzai N, Goto A, Sakamoto A, Niwa T, Kanai Y, Anders MW, Endou H: "Molecular identification of a novel carnitine transporter specific of human testis"J.Biol.Chem.. 277(39). 36262-36271 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuo, H., Kanai, Y., Kim, J.Y., Chairoungdua, A., Kim, D.K., Inatomi, J., Shigeta, Y., Ishimine, H., Chekuntode, S., Tacahmpa, K., Choi, H.W., Babu, E., Fukuda, J., Endou, H: "Identification of novel Na^+-independent acidic amino acid transporter with structural similarity to the member of heterodimeric amino acid transporter family associated with unknown heavy chains"J.Biol.Chem. 277(3). 21017-21026 (2002)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] 榎本 篤, 細山田 真, 遠藤 仁: "腎臓における尿酸輸送機構. Annual Review 腎臓2002,(伊藤克己,浅野 泰,遠藤 仁,御手洗哲也,東原英二編)"中外医学社. 4(201-204) (2003)

    • Related Report
      2002 Annual Research Report

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

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