Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Drug Metab Pharmacokinet. 2013;28(2):153-8. doi: 10.2133/dmpk.dmpk-12-rg-070. Epub 2012 Sep 4.
Urate is mainly excreted into urine in humans. Serum urate level is regulated by a urate transport system located on the renal proximal tubule. Urate transporter 1 (URAT1) is located on the apical side of the renal proximal tubule and is responsible for the reabsorption of urate from the luminal side into tubular cells. At the same site, it has been hypothesized that sodium-coupled monocarboxylate transporters (SMCTs) are responsible for the transportation of monocarboxylates such as lactate and nicotinate, which are exchanged for urate transport via URAT1. Accordingly, SMCTs could enhance URAT1-mediated urate reabsorption by providing monocarboxylates for the exchange. The present study was carried out to clarify the hypothesized functional cooperative relationship between URAT1 and SMCTs in the reabsorptive transport of urate. By preloading nicotinate in SMCT1/URAT1-coexpressing Xenopus oocytes, URAT1-mediated urate transport was stimulated. Nicotinate was taken up by SMCT1 but not by URAT1. When removing sodium ions from the uptake medium, the stimulation effect was decreased. When adding SMCT1 inhibitors, the stimulation effect was also reduced. The results from this study indicate the cooperative relationship of URAT1 and SMCT1, and that SMCT1 is a potential target for the alteration of renal handling of urate indirectly.
尿酸主要在人类体内通过尿液排泄。血清尿酸水平由位于肾脏近端小管的尿酸转运系统调节。尿酸转运蛋白 1（URAT1）位于肾脏近端小管的顶端侧，负责将尿酸从腔侧重吸收到管状细胞中。在同一部位，有人假设，单羧酸转运蛋白（SMCTs）负责单羧酸如乳酸和烟酸盐的转运，这些单羧酸通过 URAT1 进行尿酸转运的交换。因此，SMCT 可以通过提供单羧酸来增强 URAT1 介导的尿酸重吸收。本研究旨在阐明 URAT1 和 SMCTs 在尿酸重吸收转运中的假设功能协同关系。通过在 SMCT1/URAT1 共表达的非洲爪蟾卵母细胞中预先加载烟酸盐，刺激 URAT1 介导的尿酸转运。烟酸盐被 SMCT1 摄取，但不能被 URAT1 摄取。当从摄取培养基中去除钠离子时，刺激作用会降低。当添加 SMCT1 抑制剂时，刺激作用也会降低。本研究的结果表明 URAT1 和 SMCT1 之间存在协同关系，并且 SMCT1 是间接改变肾脏尿酸处理的潜在靶标。
