Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Compr Physiol. 2013 Jul;3(3):1079-123. doi: 10.1002/cphy.c110061.
The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches.
肾脏通过其近端和远端肾小管段的作用,在维持体内盐和液体平衡以及血压稳态方面发挥着基本作用。然而,近端小管被认为比远端小管发挥更重要的作用。近端小管负责重吸收约 65%的滤过负荷,以及大部分(如果不是全部)滤过的氨基酸、葡萄糖、溶质和低分子量蛋白质。近端小管还通过重吸收约 80%的滤过碳酸氢盐在调节酸碱平衡方面发挥关键作用。本文综述的目的是提供对目前对肾脏近端小管的理解的新见解和新视角,重点介绍超微结构、分子生物学、细胞和整体生理学以及潜在的信号转导机制。综述分为三个紧密相关的部分。第一部分侧重于肾单位的分类以及肾单位数量在人类健康和疾病中的潜在作用的最新观点。第二部分回顾了最近关于近端小管功能的结构和生化基础的研究。最后一部分全面概述了血管活性激素对近端小管转运的生理调节的新见解和新视角。在后一部分中,特别关注了从最近的转运体克隆、具有特定感兴趣基因敲除或敲入的转基因动物的开发以及使用微阵列和/或生理蛋白质组学方法对信号通路进行映射中获得的新见解和新视角。