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Physiological Reviews, Vol. 81, No. 1, January 2001, pp. 345-418
Copyright ©2001 by the American Physiological Society
Division of Nephrology, Geneva University Hospital, Geneva, Switzerland; and Centre National de la Recherche Scientifique Unité de Recherche Associée 1859, Service de Biologie Cellulaire, Centre d'Etudes de Saclay, Gif sur Yvette, France
Féraille, Eric and
Alain Doucet.
Sodium-Potassium-Adenosinetriphosphatase-Dependent Sodium
Transport in the Kidney: Hormonal Control. Physiol. Rev. 81: 345-418, 2001.
Tubular reabsorption of filtered sodium is quantitatively the
main contribution of kidneys to salt and water homeostasis. The
transcellular reabsorption of sodium proceeds by a two-step mechanism: Na+-K+-ATPase-energized basolateral
active extrusion of sodium permits passive apical entry through various
sodium transport systems. In the past 15 years, most of the renal
sodium transport systems (Na+-K+-ATPase,
channels, cotransporters, and exchangers) have been characterized at a
molecular level. Coupled to the methods developed during the 1965-1985
decades to circumvent kidney heterogeneity and analyze sodium transport
at the level of single nephron segments, cloning of the transporters
allowed us to move our understanding of hormone regulation of sodium
transport from a cellular to a molecular level. The main purpose of
this review is to analyze how molecular events at the transporter level
account for the physiological changes in tubular handling of sodium
promoted by hormones. In recent years, it also became obvious that
intracellular signaling pathways interacted with each other, leading to
synergisms or antagonisms. A second aim of this review is therefore to
analyze the integrated network of signaling pathways underlying hormone action. Given the central role of Na+-K+-ATPase
in sodium reabsorption, the first part of this review focuses on its
structural and functional properties, with a special mention of the
specificity of Na+-K+-ATPase expressed in renal
tubule. In a second part, the general mechanisms of hormone signaling
are briefly introduced before a more detailed discussion of the nephron
segment-specific expression of hormone receptors and signaling
pathways. The three following parts integrate the molecular and
physiological aspects of the hormonal regulation of sodium transport
processes in three nephron segments: the proximal tubule, the thick
ascending limb of Henle's loop, and the collecting duct.
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