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  • 标题:Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human
  • 本地全文:下载
  • 作者:Masanobu Sato ; Hideaki Mamada ; Naohiko Anzai
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2010
  • 卷号:33
  • 期号:3
  • 页码:498-503
  • DOI:10.1248/bpb.33.498
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:The physiological function of organic anion transporter OAT2 ( SLC22A7 ) remains unclear, but since OAT2 transports purine derivatives, it may be involved in renal handling of uric acid, the final metabolite of purine derivatives. In the present study, we studied uric acid transport in stably OAT2-expressing HEK293 cells (HEK293/OAT2). OAT2 mediated uptake, but not efflux, of [14C]uric acid. Uric acid transport was saturable with K m of 1168±335 μ M (mean and S.E.M.) and V max of 2.57±0.350 nmol/min/mg protein. The [14C]uric acid uptake was sensitive to Cl and was enhanced at acidic pH. In cis -inhibition assay, [14C]uric acid uptake was inhibited by several mono- or dicarboxylic acids, but it was not trans -stimulated by any of the compounds tested. The pattern of inhibition of OAT2-mediated uric acid transport by various drugs was different from that of OAT1- or OAT3-mediated transport. Furthermore, OAT2-mediated transport of uric acid was inhibited by an antiuricosuric drug, pyrazinecarboxylic acid. These results revealed distinct characteristics of uric acid transport via OAT2 compared with other uric acid transporters, suggesting that OAT2 plays a role in renal uric acid uptake from blood as a first step of tubular secretion. OAT2 may therefore be a potential target for regulating serum uric acid level.
  • 关键词:organic anion transporter 2;uric acid;transporter;uricosuric;antiuricosuric;serum uric acid level
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