Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human
Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human
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DOI：
10.1248/bpb.33.498
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发表时间：
2010-03-01
影响因子：
2
通讯作者：
Tamai, Ikumi
中科院分区：
文献类型：
--
作者：
Sato, Masanobu;Mamada, Hideaki;Tamai, Ikumi
有机阴离子转运体OAT2 （SLC22A7）的生理功能尚不清楚，但由于OAT2运输嘌呤衍生物，它可能参与肾脏处理尿酸，尿酸是嘌呤衍生物的最终代谢物。在本研究中，我们研究了尿酸在稳定表达OAT2的HEK293细胞（HEK293/OAT2）中的转运。OAT2介导[C-14]尿酸的摄取，而非外排。尿酸转运饱和值为1168 +/- 335 μ M（平均值和S.E.M.）， V-max为2.57 +/- 0.350 nmol/min/mg蛋白。[C-14]尿酸摄取对Cl-敏感，在酸性ph下增强。在顺式抑制试验中，[C-14]尿酸摄取被几种单羧酸或二羧酸抑制，但不受任何化合物的反式刺激。不同药物对oat2介导的尿酸转运的抑制模式不同于OAT1-或oat3介导的尿酸转运。此外，抗尿酸药物吡嗪羧酸可抑制oat2介导的尿酸转运。这些结果揭示了与其他尿酸转运蛋白相比，通过OAT2转运尿酸的独特特征，表明OAT2在肾小管分泌的第一步从血液中摄取尿酸中起作用。因此，OAT2可能是调节血清尿酸水平的潜在靶点。
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 [C-14]uric acid. Uric acid transport was saturable of 1168 +/- 335 mu M (mean and S.E.M.) and V-max of 2.57 +/- 0.350 nmol/min/mg protein. The [C-14]uric acid uptake was sensitive to Cl- and was enhanced at acidic pH. In cis-inhibition assay, [C-14]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.