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Urate transport via human voltage-driven organic anion transporter OATv1 : Mechanism for diuretics-induced hyperuricemia

Research Project

Project/Area Number 21890245
Research Category

Grant-in-Aid for Research Activity Start-up

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

Principal Investigator

JUTABHA Promsuk  Kyorin University, 医学部, 助教 (90541748)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,457,000 (Direct Cost: ¥1,890,000、Indirect Cost: ¥567,000)
Fiscal Year 2010: ¥1,092,000 (Direct Cost: ¥840,000、Indirect Cost: ¥252,000)
Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
Keywordsトランスポーター / 有機酸 / 電位依存性 / 尿酸 / 利尿薬 / パラアミノ馬尿酸
Research Abstract

Since sodium-dependent phosphate transporter NPT at the apical membrane of renal proximal tubules in human is considered to be OATv1 which mediates the extrusion of organic anions with voltage-dependent manner, I analyzed its urate-transport properties to clarify the molecular mechanism for diuretics-induced hyperuricemia targeting human OATv1. During this period, I observed voltage-dependent transport of both PAH and urate labeled with radio isotope and concentration-dependent inhibition on OATv1-mediated transport by diuretics. Thus, it is suggested that reduction of urate secretion by the competition between urate and diuretics targeting OATv1 leads to the development of diuretics-induced hyperuricemia.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (30 results)

All 2011 2010 2009

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (13 results) Book (1 results)

  • [Journal Article] Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms.2011

    • Author(s)
      Jutabha P, Anzai N, Kimura T, Taniguchi A, Urano W, Yamanaka H, Endou H, Sakurai H
    • Journal Title

      J Pharmacol Sci. 115巻

      Pages: 249-253

    • NAID

      10029892290

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Developing Potent Human Uric Acid Transporter 1 (hURAT1) Inhibitors.2011

    • Author(s)
      Wempe MF, Jutabha P, Quade B, Iwen TJ,Frick MM, Ross IR, Rice PJ, Anzai N, Endou H
    • Journal Title

      J Med Chem. 54巻

      Pages: 2701-2713

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human urate transporter 1 (hURAT1) mediates the transport of orotate.2011

    • Author(s)
      Miura D, Anzai N, Jutabha P, Chanluang S, He X, Fukutomi T, Endou H
    • Journal Title

      J Physiol Sci. 61巻

      Pages: 253-257

    • NAID

      10029050258

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms.2011

    • Author(s)
      Jutabha P
    • Journal Title

      J Pharmacol Sci

      Volume: 115 Pages: 249-253

    • NAID

      10029892290

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human sodium-phosphate transporter 4(hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.2010

    • Author(s)
      Jutabha P, Anzai N, Kitamura K, Taniguchi A, Kaneko S, Yan K, Yamada H, Shimada H, Kimura T, Katada T, Fukutomi T, Tomita K, Urano W, Yamanaka H, Seki G, Fujita T, Moriyama Y, Yamada A, Uchida S, Wempe MF, Endou H, Sakurai H
    • Journal Title

      J Biol Chem. 285巻

      Pages: 35123-35132

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters.2010

    • Author(s)
      Nakamura M, Anzai N, Jutabha P, Sato H, Sakurai H, Ichida K
    • Journal Title

      J Pharmacol Sci. 114巻

      Pages: 115-118

    • NAID

      10029890030

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel transporter of SLC22 family specifically transports prostaglandins and co-localizes with 15-hydroxyprostaglandin dehydrogenase in renal proximal tubules.2010

    • Author(s)
      Shiraya K, Hirata T, Hatano R, Nagamori S, Wiriyasermkul P, Jutabha P, Matsubara M, Muto S, Tanaka H, Asano S, Anzai N, Endou H, Yamada A, Sakurai H, Kanai Y
    • Journal Title

      J Biol Chem. 285巻

      Pages: 22141-51

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Renal solute transporters and their relevance to serum urate disorder.2010

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

      Curr Hypertens Rev. 6巻

      Pages: 148-154

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanism of ochratoxin A transport in the kidney.2010

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

      Toxin. 2巻

      Pages: 1381-1398

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney.2010

    • Author(s)
      Tsuchida H, Anzai N, Shin HJ, Wempe MF, Jutabha P, Enomoto A, Cha SH, Satoh T, Sakurai H, Endou H
    • Journal Title

      Cell Physiol Biochem. 25巻

      Pages: 511-522

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Xenopus laevis oocytes expressing human P-glycoprotein : probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux.2010

    • Author(s)
      Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H
    • Journal Title

      Pharmacol Res. 61巻

      Pages: 76-84

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.2010

    • Author(s)
      Jutabha P
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 35123-35132

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters.2010

    • Author(s)
      Nakamura M
    • Journal Title

      J Pharmacol Sci

      Volume: 114 Pages: 115-118

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xenopus laevis oocytes expressing human P-glycoprotein : probing trans- and cis-inhibitory effects on[3H]vinblastine and[3H]digoxin efflux.2010

    • Author(s)
      Jutabha P
    • Journal Title

      Pharmacol Res 61

      Pages: 76-84

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney.2010

    • Author(s)
      Tsuchida H
    • Journal Title

      Cell Physiol Biochem 25

      Pages: 511-522

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新規尿酸排出トランスポーターURATv1の尿酸輸送特性の解析2009

    • Author(s)
      木村徹
    • Journal Title

      痛風と核酸代謝 33

      Pages: 177-183

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Apical voltage-driven urate efflux transporter NPT4 in renal proximal tubule. Session 8 Transport of Purine and Pyrimidine.2011

    • Author(s)
      Promsuk Jutabha
    • Organizer
      14^<th> International Symposium on Purine and Pyrimidine Metabolism in Man, PP11
    • Place of Presentation
      新宿
    • Year and Date
      2011-02-20
    • Related Report
      2010 Final Research Report
  • [Presentation] Apical voltage-driven urate efflux transporter NPT4 in renal proximal tubule.2011

    • Author(s)
      Jutabha Promsuk
    • Organizer
      14th International Symposium on Purine and Pyrimidine Metabolism in Man, PP11
    • Place of Presentation
      新宿
    • Year and Date
      2011-02-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] A novel human urate/anion exchanger URAT2 identified as a novel target of uricosuric agents2010

    • Author(s)
      Promsuk Jutabha
    • Organizer
      20^<th> Japan-Korea Joint Seminar on Pharmacology
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] A novel human urate/anion exchanger URAT2 identified as a novel target of uricosuric agents2010

    • Author(s)
      Promsuk Jutabha
    • Organizer
      第123回日本薬理学会関東部会
    • Place of Presentation
      宇都宮
    • Year and Date
      2010-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutations in renal drug efflux transporter hOATv1 cause hyperuricemia2010

    • Author(s)
      Promsuk Jutabha
    • Organizer
      Experimental Biology 2010
    • Place of Presentation
      Anaheim
    • Year and Date
      2010-04-25
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutations in renal drug efflux transporter hOATv1 cause hyperuricemia2010

    • Author(s)
      Promsuk Jutabha
    • Organizer
      14^<th> International Congress of Endocrinology
    • Place of Presentation
      京都
    • Year and Date
      2010-03-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 新規ヒト電位依存性有機酸トランスポーターhOATv1の分子同定:ループ利尿薬排出経路の解明2009

    • Author(s)
      Promsuk Jutabha
    • Organizer
      トランスポーター研究会第3回九州部会
    • Place of Presentation
      鹿児島
    • Year and Date
      2009-11-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular identification of a novel human voltage-driven organic anion transporter hOATv1 : a luminal exit path of loop diuretics.2009

    • Author(s)
      Promsuk Jutabha
    • Organizer
      American Society of Nephrology Renal Week 2009
    • Place of Presentation
      San Diego
    • Year and Date
      2009-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] アフリカツメガエル卵母細胞における新規ヒト尿酸排出トランスポーターURATv1の電位依存性尿酸輸送特性の解析2009

    • Author(s)
      Promsuk Jutabha
    • Organizer
      第82回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular identification of a novel human voltage-driven organic anion transporter hOATv1 : a luminal exit path of loop diuretics2009

    • Author(s)
      Promsuk Jutabha
    • Organizer
      第15回分子腎臓研究会
    • Place of Presentation
      京都
    • Year and Date
      2009-09-05
    • Related Report
      2010 Final Research Report
  • [Presentation] Molecular identification of a novel human voltage-driven organic anion transporter hOATv1 : a luminal exit path of loop diuretics2009

    • Author(s)
      Jutabha Promsuk
    • Organizer
      第15回分子腎臟研究会
    • Place of Presentation
      京都
    • Year and Date
      2009-09-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] The voltage-driven organic anion transport of type I sodium-phosphate cotransporter and OATv12009

    • Author(s)
      Promsuk JUTABHA
    • Organizer
      36^<th> International Congress of Physiological Sciences
    • Place of Presentation
      京都
    • Year and Date
      2009-07-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Neutral amino acid uptake in epithelial cells and its diseases : novel amino acid transporter SLC6 family2009

    • Author(s)
      Promsuk Jutabha
    • Organizer
      第4回トランスポーター研究会年会シンポジウムII
    • Place of Presentation
      文京区
    • Year and Date
      2009-05-24
    • Related Report
      2010 Final Research Report
  • [Book] 薬物トランスポーター2009

    • Author(s)
      安西尚彦
    • Total Pages
      3
    • Publisher
      羊土社
    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2021-04-07  

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