Knepper M A, Star R A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Physiol. 1990 Sep;259(3 Pt 2):F393-401. doi: 10.1152/ajprenal.1990.259.3.F393.
The terminal part of the inner medullary collecting duct (terminal IMCD) is unique among collecting duct segments in part because its permeability to urea is regulated by vasopressin. The urea permeability can rise to extremely high levels (greater than 100 x 10(-5) cm/s) in response to vasopressin. Recent studies in isolated perfused IMCD segments have established that the rapid movement of urea across the tubule epithelium occurs via a specialized urea transporter, presumably an intrinsic membrane protein, present in both the apical and basolateral membranes. This urea transporter has properties similar to those of the urea transporters in mammalian erythrocytes and in toad urinary bladder, namely, inhibition by phloretin, inhibition by urea analogues, saturation kinetics in equilibrium-exchange experiments, and regulation by vasopressin. The urea transport pathway is distinct from and independent of the vasopressin-regulated water channel. The increase in transepithelial urea transport in response to vasopressin is mediated by adenosine 3',5'-cyclic monophosphate and is associated with an increase in the urea permeability of the apical membrane. However, little is known about the physical events associated with the activation or insertion of urea transporters in the apical membrane. Because of the importance of this transporter to the urinary concentrating mechanism, efforts toward understanding its molecular structure and the molecular basis of its regulation appear to be justified.
髓质内集合管终末段（终末IMCD）在集合管各节段中独具特色，部分原因在于其对尿素的通透性受血管升压素调节。响应血管升压素时，尿素通透性可升至极高水平（大于100×10⁻⁵ cm/s）。近期对分离灌注的IMCD节段的研究证实，尿素在肾小管上皮细胞间的快速转运是通过一种特殊的尿素转运体实现的，推测该转运体是一种内在膜蛋白，存在于顶端膜和基底外侧膜中。这种尿素转运体具有与哺乳动物红细胞及蟾蜍膀胱中的尿素转运体相似的特性，即受根皮素抑制、受尿素类似物抑制、在平衡交换实验中呈现饱和动力学，以及受血管升压素调节。尿素转运途径与血管升压素调节的水通道不同且相互独立。血管升压素引起的跨上皮尿素转运增加由3',5'-环磷酸腺苷介导，并与顶端膜尿素通透性增加相关。然而，对于与顶端膜中尿素转运体激活或插入相关的物理事件知之甚少。鉴于该转运体对尿液浓缩机制的重要性，致力于了解其分子结构及其调节的分子基础似乎是合理的。
