Department of Membrane Transport and Biopharmaceutics, Kanazawa University, Kakuma-machi, Kanazawa , Japan.
Nephrol Dial Transplant. 2013 Mar;28(3):603-11. doi: 10.1093/ndt/gfs574. Epub 2013 Jan 4.
Serum urate (SUA) level is affected by alteration in urinary reabsorption caused by clinically important drugs; however, there are no experimental models suitable to assess their effect on renal reabsorption. We, therefore, aimed to establish an experimental system co-expressing the urate transporters URAT1 (SLC22A12) and URATv1 (SLC2A9) (designated UUv cells) at the apical and basolateral membranes, respectively.
Apical uptake and vectorial transport of [(14)C]urate in the apical-to-basolateral direction in UUv cells were measured in the presence or absence of uricosuric benzbromarone or anti-uricosuric trans-stimulators.
The urate permeability in the apical-to-basolateral direction remarkably increased by 7.0-fold in UUv cells, compared with non-transfected mock cells. The apical-to-basolateral transport was cis-inhibited by benzbromarone, but trans-stimulated by pyrazinecarboxylic acid and monocarboxylates such as nicotinate and lactate. Furthermore, salicylate showed both trans-stimulation and cis-inhibition in the urate transport at low and high concentrations, respectively. Finally, coexpression of URAT1 and URATv1 in human kidney epithelial cells was exhibited immunohistochemically.
It is demonstrated that functional cooperation of URAT1 and URATv1 is essential for renal reabsorption of urate, and in the established system influence of drugs on SUA is reflected in the alteration of urate permeability across the renal tubular epithelial cells.
血清尿酸（SUA）水平受临床重要药物引起的尿液重吸收改变的影响；然而，目前还没有合适的实验模型来评估它们对肾重吸收的影响。因此，我们旨在建立一个分别在顶侧和基底外侧膜共表达尿酸转运体 URAT1（SLC22A12）和 URATv1（SLC2A9）的实验系统（命名为 UUv 细胞）。
在存在或不存在尿酸排泄促进剂苯溴马隆或抗尿酸转运体转导刺激物的情况下，测量 [(14)C]尿酸在 UUv 细胞中的顶侧到基底外侧方向的摄取和向量转运。
与未转染的 mock 细胞相比，UUv 细胞中尿酸在顶侧到基底外侧方向的通透性显著增加了 7.0 倍。苯溴马隆对顶侧到基底外侧的转运具有顺式抑制作用，但对吡嗪羧酸和单羧酸如烟酸盐和乳酸盐具有反式刺激作用。此外，水杨酸盐在低浓度和高浓度下分别对尿酸转运具有反式刺激和顺式抑制作用。最后，在人肾上皮细胞中显示了 URAT1 和 URATv1 的共表达。
功能性 URAT1 和 URATv1 的合作对于尿酸的肾重吸收是必要的，并且在建立的系统中，药物对 SUA 的影响反映在尿酸通过肾小管上皮细胞的通透性的改变上。
