Sodium-Potassium-Adenosinetriphosphatase-Dependent Sodium Transport in the Kidney: Hormonal Control
摘要:
I. INTRODUCTION Mammalian kidneys play a major role in the homeostasis of extracellular compartment. Despite large qualitative and quantitative variations in dietary intake of salutes and water, the kidneys are able to maintain the composition and the volume of the extracellular compartment within very narrow margins. This homeostatic function of kidneys requires the presence of numbers of specific carriers able to transport a large variety of substrates and their fine control by specific factors and hormones. Since the onset of modem renal physiology, tremendous efforts have been made to describe the transport properties of the kidney tubule and to analyze their regulatory factors. This led, in the mid 1980s, to an almost coherent cellular description of the transport properties of the successive segments constituting the nephron, as well as to the localization and characterization of hormonal regulation of these processes [566]. During the past 10-15 years, most efforts have permitted the evolution from this cellular level of understanding to a molecular one. This evolution mainly results from 1) the molecular cloning of membrane transporters and hormone receptors involved in solute and water transport and its regulation, 2) the characterization of new extracellular regulatory factors and deciphering of new intracellular signaling pathways, 3) the acknowledgement that intracellular signaling pathways should not be considered as linear and parallel chains of interactions, but as intricated and interactive networks. Such combinatorial organization markedly increases the diversity of signaling. 4) Lastly, the idea has slowly emerged that the cornerstone of kidney transport machinery, [Na.sup.+] - [K.sup.+]-ATPase, is not a house-keeping protein that does not participate actively to rapid adaptations of kidney function but is an important molecular target of hormonal regulation. For this last reason, we have chosen to take [Na.sup.+] - [K.sup.+]-ATPase as a leading thread in the analysis of the hormonal control of sodium transport in the kidney. This review has been focused on the regulatory pathways of sodium transport that share the following criteria: 1) mechanisms are deciphered, at least partially, at the molecular level; 2) transport is dependent on [Na.sup.+] - [K.sup.+]-ATPase; and 3) transport mechanism has a functional relevance with sodium homeostasis. In the two first sections of this review, we summarize the general properties and the renal specificities of [Na.sup.+] - [K.sup.+]-ATPase and of intracellular signaling pathways. The three following parts are devoted to the hormonal regulation of cation transport in proximal tubule, thick ascending limb of Henle's loop, and collecting duct. For each structure, the cellular and molecular mechanisms of sodium transport are analyzed before discussing the actions of the main hormones. For each hormone, the general physiological response is first described, and then the regulation of [Na.sup.+] - [K.sup.+]-ATPase and other transporters is analyzed in terms of intrinsic changes in properties and of signaling mechanisms. II. SODIUM-POTASSIUM-ADENOSINETRIPHOSPHATASE IN SODIUM TRANSPORT ALONG THE RENAL TUBULE Epithelial cell layers separate compartments of distinct compositions and ensure transfer of water and solutes between them. The serosal compartment, in equilibrium with blood plasma, is characterized by the constancy of its composition....
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DOI:
10.1086/319299
被引量:
年份:
2001


































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