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Role of a novel prostaglandin transporter OAT-PG in sodium transport regulation mechanism

Research Project

Project/Area Number 18590900
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

ANZAI Naohiko  Kyorin University, Sch. of Med. Dept. of Pharmacol. and Toxicol, Lecturer (70276054)

Co-Investigator(Kenkyū-buntansha) KANAI Yoshikatsu  Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Professor (60204533)
HIRATA Taku  Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Assistant Professor (60372918)
FUKUTOMI Toshiyuki  Kyorin Univ., Sch. of Med. Dept. of Pharmacol. and Toxicol, Assistant Professor (30439187)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsProstaglandin / Kidney / Cyclooxigenase / Anions / Transporter / COX-2 / PDZ / PDZ proteins
Research Abstract

In the kidney, prostaglandins (PGs), especially prostaglandin E_2(PGE_2), have important roles in renal hemodynamics, renin release, tubular sodium and water reabsorption. Because PGs are charged organic anions at physiological pH, they poorly penetrate biological membranes. Accordingly, PG transport is a carrie瀕ediated process. So far only prostaglandin transporter (PGT) from OATP (SLC0/SLC21) family is known as a transporter specific to PGs. Recently, we isolated a cDNA encoding a novel prostaglandin-specific transporter from mouse kidney. Because this transporter belongs to organic anion transporter (OAT) family (SLC22) structurally distinct from PGT, we named this prostaglandin-specific organic anion transporter (OAT-PG). OAT-PG specifically mediated a transport of PGs such as PGE_2 and PGF_<2a>. It was speculated that OAT-PG plays an important role in renal handling of PGE_2 and contributes to physiological functions involving in PGE_2 metabolism. Particularly, through the interac … More tion with COX-2 and EP4 receptor, PGE_2 may function as a signaling molecule that regulates the sodium transport at the distal segments of nephron.
This study was performed to examine the possibility that OAT-PG constitute the renal apical prostaglandin signaling mechanism. First, we investigate the driving force of OAT-PG-mediated PGs transport because in in vitro PG transport via OAT-PG seems bidirectional By using trans-stimulatory experiments, we identified that inorganic sulfate ion may be a counter ion for OATPG-mediated PGs transport. Next, to confirm that the components of renal apical PG signaling such as OATPG, COX-2and EP4 are tethered by some kind of scaffolding protein (s), we perfomed the yeast two-hybrid screening of kidney cDNA library using OATPG C-terminal sequence as bait. From this screening, we succeeded to identify that multivalent PDZ-domain protein CIPP (Channel-Interacting PDZ protein) is the binding partner of OAT-PG. These results will contribute to the clarification of renal apical PG signaling mechanism surrounding OAT-PG. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (29 results)

All 2008 2007 2006

All Journal Article (19 results) (of which Peer Reviewed: 4 results) Presentation (9 results) Book (1 results)

  • [Journal Article] Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans2008

    • Author(s)
      Anzai N
    • Journal Title

      J Biol Chem 283

      Pages: 26834-26838

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Plasma urate level is directly regulated by a voltage-driven urate efflux transporter uratvl (slc2a9) in humans.2008

    • Author(s)
      Anzai N. Ichida K, Jutabha P, Kimura T, Babu E, Jin CJ, Srivastava S, Kitamura K, Hisatome I, Endou H, Sakurai H.
    • Journal Title

      J Biol Chem. 283

      Pages: 26834-26838

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9) in rat renal collecting duct.2008

    • Author(s)
      Yokoyama H, Anzai N. Ljubojevic M, Ohtsu N, Sakata T, Miyazaki H, Nonoguchi H, Islam R, Onozato M, Tojo A, Tomita K, Kanai Y, Igarashi T, Sabolic I, Endou H.
    • Journal Title

      Cell Physiol Biochem. 21

      Pages: 269-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 膜輸送蛋白質Up-to-Date2008

    • Author(s)
      安西 尚彦
    • Journal Title

      日本腎臓学会誌 50

      Pages: 110-113

    • NAID

      10024900277

    • Related Report
      2007 Annual Research Report
  • [Journal Article] New insights into renal transport of urate.2007

    • Author(s)
      Anzai N
    • Journal Title

      Curr Opin Rheumatol 19

      Pages: 151-157

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate2007

    • Author(s)
      Shin HJ
    • Journal Title

      Hepatology 45

      Pages: 1046-1055

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport.2007

    • Author(s)
      Cunningham R, Brazie M, Kanumuru S, E X, Biswas R, Wang F, Steplock D, Wade JB, Anzai N. Endou H, Shenolikar S, Weinman EJ.
    • Journal Title

      J Am Soc Nephrol. 18

      Pages: 1419-1425

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate.2007

    • Author(s)
      Shin HJ, Anzai N, Enomoto A, He X, Kim do K, Endou H, Kanai Y.
    • Journal Title

      Hepatology. 45

      Pages: 1046-1055

    • NAID

      130005449292

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] New insights into renal transport of urate.2007

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

      Curr Opin Rheumatol. 19

      Pages: 151-157

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of mouse organic anion transporter 3 (m0at3) as a basolateral prostaglandin E2 transport pathway.2007

    • Author(s)
      Nilwarangkoon S, Anzai N. Shiraya K, Yu E, Islam R, Cha SH, Onozato ML, Miura D, Jutabha P, Tojo A, Kanai Y, Endou H.
    • Journal Title

      J Pharmacol Sci. 103

      Pages: 48-55

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sodium-hydrogen exchanger regulatory factor-1 interacts with mouse urate transporter 1 to regulate renal proximal tubule uric acid transport.2007

    • Author(s)
      Cunningham R
    • Journal Title

      J Am Soc Nephrol 18

      Pages: 1419-1425

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of mouse organic anion transporter 3 (mOat3) as a basolateral prostaglandin E2 transport pathway.2007

    • Author(s)
      Nilwarangkoon S
    • Journal Title

      J Pharmacol Sci. 103・1

      Pages: 48-55

    • Related Report
      2006 Annual Research Report
  • [Journal Article] New insights into renal transport of urate.2007

    • Author(s)
      Anzai N
    • Journal Title

      Curr Opin Rheumatol. 19・2

      Pages: 151-157

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification and characterization of a novel renal prostaglandin-specific organic anion transporter (OAT-PG) structurally distinct from PGT.2006

    • Author(s)
      Anzai N, Shiraya K, Hirata T, Jutabha P, Hatano R, Sanada S, Matsubara M, MutoS, Endou H, Lanai Y.
    • Journal Title

      J Pharmacol Sci. 100

      Pages: 111-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Organic anion transporter family : current knowledge2006

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

      J Pharmacol Sci. 100

      Pages: 411-426

    • NAID

      10018238661

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells.2006

    • Author(s)
      Asif AR
    • Journal Title

      Am J Physiol Endocrinol Metab 291・6

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Organic anion transporter family : current knowledge.2006

    • Author(s)
      Anzai N
    • Journal Title

      J Pharmacol Sci. 100・5

      Pages: 411-426

    • NAID

      10018238661

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The PDZ domain protein PDZK1 interacts with human peptide transporter PEPT2 and enhances its transport activity.2006

    • Author(s)
      Noshiro R
    • Journal Title

      Kidney Int. 70・2

      Pages: 275-282

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of rat renal cortical OAT1 and OAT3 in response to acute biliary obstruction.2006

    • Author(s)
      Brandoni A
    • Journal Title

      Hepatology. 43・5

      Pages: 1092-1100

    • Related Report
      2006 Annual Research Report
  • [Presentation] Interaction of the multivalent PDZ "domain protein PDZK1 with novel liver-specific organic anion transporter 72008

    • Author(s)
      Anzai N. Shin H, Miyao K, Endou H
    • Organizer
      Experimental Biology 2008
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2008-04-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Renal Drug Transporters and Nephrotoxicity2007

    • Author(s)
      Naohiko Anzai. Hitoshi Endou
    • Organizer
      6th World Congress on Alternatives & Animal Use in the Life Sciences
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-08-22
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 有機イオンの細胞膜輸送 : トランスポーターの基礎と臨床2007

    • Author(s)
      安西 尚彦
    • Organizer
      第3回JPC/JCNRA合同プテリジン研究会
    • Place of Presentation
      東京都板橋区
    • Year and Date
      2007-07-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Transcellular transport of organic ions: Basic and clinical importance of transporters2007

    • Author(s)
      Naohiko Anzai
    • Organizer
      3^<rd> joint meeting of JPC/JCNRA
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2007-07-21
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 有機イオンの細胞膜輸送:トランスポーターの基礎と臨床2007

    • Author(s)
      安西 尚彦
    • Organizer
      第3回JPC/JCNRA合同プテリジン研究会
    • Place of Presentation
      東京都板橋区
    • Year and Date
      2007-07-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] Heterodimeric amino acid transporters : protein-protein interactions for membrane targeting cellular signaling2007

    • Author(s)
      Yoshikatsu Kanai, Naohiko Anzai. Taku Hirata, Takeshi Ueno, Toru Kimura, Toshiyuki Fukutomi, Arthit Chairoungdua
    • Organizer
      Joint International Symposium Membrane Transport as a Universal Biological Mechanism
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2007-01-13
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Immunolocalization of G-protein-coupled receptors for succinate (GPR91) and a -ketoglutarate (GPR99) in the human nephron2007

    • Author(s)
      Naohiko Anzai, Vedran Micek, Hrvoje Brzica, Hermann Koepsell, Ivan Sabolic
    • Organizer
      5th International Symposium on receptor Mechanisms, Signal Transduction and drug Effects
    • Place of Presentation
      Shizuoka, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Identification of the multivalent PDZ domain protein PDZKl as a binding partner of sodium-coupled monocarboxylate cotransporter 1 (SMCT1).2006

    • Author(s)
      Naohiko Anzai, Hiroki Miyazaki, Xin He, Yoshikatsu Kanai, Seiji Miyauchi, Vadivel Ganapathy
    • Organizer
      American Society of Nephrology Renal Week 2006
    • Place of Presentation
      San Diego
    • Year and Date
      2006-11-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Involvement of transporters in nephrotoxicity.2006

    • Author(s)
      Endou H, Anzai N
    • Organizer
      15th World Congress of Pharmacology (IUPHAR)
    • Place of Presentation
      Beijing, China
    • Year and Date
      2006-07-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Drug transport in the kidney2007

    • Author(s)
      Naohiko Anzai
    • Total Pages
      30
    • Publisher
      John Wiley & Sons, Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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