Pearce David, Soundararajan Rama, Trimpert Christiane, Kashlan Ossama B, Deen Peter M T, Kohan Donald E
Division of Nephrology, Department of Medicine, University of California, San Francisco, California;
Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas;
Clin J Am Soc Nephrol. 2015 Jan 7;10(1):135-46. doi: 10.2215/CJN.05760513. Epub 2014 May 29.
The principal cell of the kidney collecting duct is one of the most highly regulated epithelial cell types in vertebrates. The effects of hormonal, autocrine, and paracrine factors to regulate principal cell transport processes are central to the maintenance of fluid and electrolyte balance in the face of wide variations in food and water intake. In marked contrast with the epithelial cells lining the proximal tubule, the collecting duct is electrically tight, and ion and osmotic gradients can be very high. The central role of principal cells in salt and water transport is reflected by their defining transporters-the epithelial Na(+) channel (ENaC), the renal outer medullary K(+) channel, and the aquaporin 2 (AQP2) water channel. The coordinated regulation of ENaC by aldosterone, and AQP2 by arginine vasopressin (AVP) in principal cells is essential for the control of plasma Na(+) and K(+) concentrations, extracellular fluid volume, and BP. In addition to these essential hormones, additional neuronal, physical, and chemical factors influence Na(+), K(+), and water homeostasis. Notably, a variety of secreted paracrine and autocrine agents such as bradykinin, ATP, endothelin, nitric oxide, and prostaglandin E2 counterbalance and limit the natriferic effects of aldosterone and the water-retaining effects of AVP. Considerable recent progress has improved our understanding of the transporters, receptors, second messengers, and signaling events that mediate principal cell responses to changing environments in health and disease. This review primarily addresses the structure and function of the key transporters and the complex interplay of regulatory factors that modulate principal cell ion and water transport.
肾集合管主细胞是脊椎动物中调控最为严格的上皮细胞类型之一。激素、自分泌和旁分泌因子对主细胞转运过程的调节作用，对于在食物和水摄入量变化很大的情况下维持体液和电解质平衡至关重要。与近端小管内衬的上皮细胞形成鲜明对比的是，集合管的电导率很低，离子和渗透梯度可能非常高。主细胞在盐和水转运中的核心作用通过其标志性转运蛋白得以体现，即上皮钠通道（ENaC）、肾外髓质钾通道和水通道蛋白2（AQP2）水通道。醛固酮对ENaC的协调调节以及精氨酸加压素（AVP）对主细胞中AQP2的调节，对于控制血浆钠和钾浓度、细胞外液量和血压至关重要。除了这些必需激素外，其他神经、物理和化学因素也会影响钠、钾和水平衡。值得注意的是，多种分泌的旁分泌和自分泌因子，如缓激肽、ATP、内皮素、一氧化氮和前列腺素E2，会抵消并限制醛固酮的排钠作用和AVP的保水作用。最近取得的显著进展增进了我们对介导主细胞在健康和疾病状态下对变化环境做出反应的转运蛋白、受体、第二信使和信号转导事件的理解。本综述主要探讨关键转运蛋白的结构和功能，以及调节主细胞离子和水转运的调节因子之间的复杂相互作用。
