Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human

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Author(s)

Abstract

The physiological function of organic anion transporter OAT2 (<i>SLC22A7</i>) 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 [<sup>14</sup>C]uric acid. Uric acid transport was saturable with <i>K</i><sub>m</sub> of 1168±335 μ<small>M</small> (mean and S.E.M.) and <i>V</i><sub>max</sub> of 2.57±0.350 nmol/min/mg protein. The [<sup>14</sup>C]uric acid uptake was sensitive to Cl<sup>−</sup> and was enhanced at acidic pH. In <i>cis</i>-inhibition assay, [<sup>14</sup>C]uric acid uptake was inhibited by several mono- or dicarboxylic acids, but it was not <i>trans</i>-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 <i>via</i> 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.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 33(3), 498-503, 2010

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130000248105
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    10582662
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
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