Alternative channels for urea in the inner medulla of the rat kidney.
Alternative channels for urea in the inner medulla of the rat kidney.
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大鼠肾脏内髓质中尿素的替代通道。
DOI：
10.1152/ajprenal.00392.2015
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Pannabecker,ThomasL
中科院分区：
文献类型：
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作者：
Nawata,CMichele;Dantzler,WilliamH;Pannabecker,ThomasL
在大鼠的延髓内侧的亨利氏袢的上行细肢（ATL）和下行细肢（DTLs）对尿素具有高度的渗透性，但在这些切片中尚未发现尿素转运蛋白。我们推测，在这些肾小管段的新的，尚未确定的转运蛋白可以解释高尿素渗透性。从Munich-Wistar大鼠内髓中分离并克隆了编码Na+-葡萄糖转运蛋白1a（SGLT 1a）、Na+-葡萄糖转运蛋白1（NaGLT 1）、尿素转运蛋白（UT）-A2 c和UT-A2 d的cDNA。SGLT 1a是SGLT 1的一种新型NH 2-末端截短变体。NaGLT 1是一种Na+依赖性葡萄糖转运蛋白，主要位于近端小管中，之前未在细肢中描述过。UT-A2 c和UT-A2 d是UT-A2的新变体。UT-A2 c在COOH末端被截短，UT-A2 d具有一个外显子被跳过。当大鼠进行限水72 h时，ATL中SGLT 1a的mRNA水平增加，ATL和DTLs中NaGLT 1水平增加，ATL中UT-A2 c增加。在异源表达这些蛋白质的异种卵母细胞上进行的[14 C]尿素摄取试验显示，尽管与其全长版本存在结构差异，但SGLT 1a、UT-A2 c和UT-A2 d增强了尿素摄取。NaGLT 1也促进尿素吸收。吸收Na+的独立性和可通过根皮素和/或根皮苷。我们的数据表明，有几个替代渠道的尿素在大鼠内髓质，可能有助于高尿素渗透性薄肢体节段。
The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's loop in the inner medulla of the rat are highly permeable to urea, and yet no urea transporters have been identified in these sections. We hypothesized that novel, yet-unidentified transporters in these tubule segments could explain the high urea permeability. cDNAs encoding for Na+-glucose transporter 1a (SGLT1a), Na+-glucose transporter 1 (NaGLT1), urea transporter (UT)-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel NH2-terminal truncated variant of SGLT1. NaGLT1 is a Na+-dependent glucose transporter primarily located in the proximal tubules and not previously described in the thin limbs. UT-A2c and UT-A2d are novel variants of UT-A2. UT-A2c is truncated at the COOH terminus, and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in ATLs, NaGLT1 levels increased in both ATLs and DTLs, and UT-A2c increased in ATLs. [14C]urea uptake assays performed onXenopusoocytes heterologously expressing these proteins revealed that despite having structural differences from their full-length versions, SGLT1a, UT-A2c, and UT-A2d enhanced urea uptake. NaGLT1 also facilitated urea uptake. Uptakes were Na+independent and inhibitable by phloretin and/or phloridzin. Our data indicate that there are several alternative channels for urea in the rat inner medulla that could potentially contribute to the high urea permeabilities in thin limb segments.