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

• Project/Area Number: 21890245
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Kyorin 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [Presentation] A novel human urate/anion exchanger URAT2 identified as a novel target of uricosuric agents (2010)
  • 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
• [Presentation] A novel human urate/anion exchanger URAT2 identified as a novel target of uricosuric agents (2010)
  • 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
• [Presentation] Mutations in renal drug efflux transporter hOATv1 cause hyperuricemia (2010)
  • Author(s): Promsuk Jutabha
  • Organizer: Experimental Biology 2010
  • Place of Presentation: Anaheim
  • Year and Date: 2010-04-25
• [Presentation] Mutations in renal drug efflux transporter hOATv1 cause hyperuricemia (2010)
  • Author(s): Promsuk Jutabha
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: 京都
  • Year and Date: 2010-03-28
• [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
• [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
• [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
• [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: 第15回分子腎臓研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-09-05
• [Presentation] Molecular identification of a novel human voltage-driven organic anion transporter hOATv1 : a luminal exit path of loop diuretics (2009)
  • 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
• [Presentation] The voltage-driven organic anion transport of type I sodium-phosphate cotransporter and OATv1 (2009)
  • Author(s): Promsuk JUTABHA
  • Organizer: 36^<th> International Congress of Physiological Sciences
  • Place of Presentation: 京都
  • Year and Date: 2009-07-29
• [Presentation] Neutral amino acid uptake in epithelial cells and its diseases : novel amino acid transporter SLC6 family (2009)
  • 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
• [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