Urea Transport in the Kidney
Urea Transport in the Kidney
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DOI：
10.1002/cphy.c100030
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发表时间：
2011-04-01
影响因子：
5.8
通讯作者：
Sands, Jeff M.
中科院分区：
文献类型：
--
作者：
Klein, Janet D.;Blount, Mitsi A.;Sands, Jeff M.
20世纪80年代末，尿素转运蛋白最初被认为存在于肾脏中，当时尿素渗透性研究显示其值超过了简单脂相扩散和细胞旁转运的预测值。不到十年后，第一个尿素转运蛋白被克隆出来。目前，尿素转运蛋白的SLC 14 A家族包含两个主要亚组：SLC 14 A1，最初从红细胞分离的UT-B尿素转运蛋白;和SLC 14 A2，迄今为止描述的具有六种不同亚型的UT-A组。在肾脏中，UT-A1和UT-A3存在于内髓集合管中; UT-A2位于细的降支中，UT-B主要位于降直血管中;都是糖蛋白。这些转运蛋白对肾脏浓缩尿液的能力至关重要。UT-A1和UT-A3受加压素的急性调节。UT-A1也被证明受高渗、血管紧张素II和催产素的调节。这些转运蛋白的急性调节是通过磷酸化。UT-A1和UT-A3均响应于加压素或高渗性的刺激而在质膜中快速积累。长期调节包括改变蛋白质丰度以响应水合状态、低蛋白饮食、肾上腺类固醇、持续利尿或抗利尿的变化。尿素转运蛋白已被研究使用动物模型的疾病，包括糖尿病，锂中毒，高血压，肾毒性药物反应。正在开发令人兴奋的新动物模型来研究这些转运蛋白并寻找活性尿素转运蛋白。在这里，我们介绍尿素和描述尿素转运蛋白，其调节，以及它们在肾脏中的作用的现有知识。(C)2011年美国生理学会。Compr Physiol 1：699-729，2011.
Urea transport proteins were initially proposed to exist in the kidney in the late 1980s when studies of urea permeability revealed values in excess of those predicted by simple lipid-phase diffusion and paracellular transport. Less than a decade later, the first urea transporter was cloned. Currently, the SLC14A family of urea transporters contains two major subgroups: SLC14A1, the UT-B urea transporter originally isolated from erythrocytes; and SLC14A2, the UT-A group with six distinct isoforms described to date. In the kidney, UT-A1 and UT-A3 are found in the inner medullary collecting duct; UT-A2 is located in the thin descending limb, and UT-B is located primarily in the descending vasa recta; all are glycoproteins. These transporters are crucial to the kidney's ability to concentrate urine. UT-A1 and UT-A3 are acutely regulated by vasopressin. UT-A1 has also been shown to be regulated by hypertonicity, angiotensin II, and oxytocin. Acute regulation of these transporters is through phosphorylation. Both UT-A1 and UT-A3 rapidly accumulate in the plasma membrane in response to stimulation by vasopressin or hypertonicity. Long-term regulation involves altering protein abundance in response to changes in hydration status, low protein diets, adrenal steroids, sustained diuresis, or antidiuresis. Urea transporters have been studied using animal models of disease including diabetes mellitus, lithium intoxication, hypertension, and nephrotoxic drug responses. Exciting new animal models are being developed to study these transporters and search for active urea transporters. Here we introduce urea and describe the current knowledge of the urea transporter proteins, their regulation, and their role in the kidney. (C) 2011 American Physiological Society. Compr Physiol 1: 699-729, 2011.