論文

査読有り
2010年11月

Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Promsuk Jutabha
  • ,
  • Naohiko Anzai
  • ,
  • Kenichiro Kitamura
  • ,
  • Atsuo Taniguchi
  • ,
  • Shuji Kaneko
  • ,
  • Kunimasa Yan
  • ,
  • Hideomi Yamada
  • ,
  • Hidetaka Shimada
  • ,
  • Toru Kimura
  • ,
  • Tomohisa Katada
  • ,
  • Toshiyuki Fukutomi
  • ,
  • Kimio Tomita
  • ,
  • Wako Urano
  • ,
  • Hisashi Yamanaka
  • ,
  • George Seki
  • ,
  • Toshiro Fujita
  • ,
  • Yoshinori Moriyama
  • ,
  • Akira Yamada
  • ,
  • Shunya Uchida
  • ,
  • Michael F. Wempe
  • ,
  • Hitoshi Endou
  • ,
  • Hiroyuki Sakurai

285
45
開始ページ
35123
終了ページ
35132
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M110.121301
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4.

Web of Science ® 被引用回数 : 80

リンク情報
DOI
https://doi.org/10.1074/jbc.M110.121301
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000283659100086&DestApp=WOS_CPL

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