Mediators of aldosterone action in the renal tubule.
The aldosterone-sensitive distal nephron extends from the second part of the distal convoluted tubule to the inner medullary collecting duct. As recently shown, aldosterone increases within two hours the abundance of the alpha-subunit of the epithelial sodium channel along the entire aldosterone-sensitive distal nephron, whereas it induces only in an initial portion of the aldosterone-sensitive distal nephron an apical translocation of all three epithelial sodium channel subunits. This suggests that another factor or factors determines the length of the aldosterone-sensitive distal nephron portion in which aldosterone controls epithelial sodium channel surface expression. Since the glucocorticoid-induced kinase SGK1 was identified as aldosterone-induced protein in 1999, it has been postulated to play a key regulatory role. The in-vivo localization of its induction to segment-specific cells of the aldosterone-sensitive distal nephron, and the in-vitro correlation of the amount of its hyperphosphorylated form with transepithelial sodium transport, support this hypothesis. Other recent studies unravel pathways other than those activated by aldosterone and insulin that impact on SGK1 expression and/or function, and thus shed some light onto the complex network that appears to control sodium transport. In view of the ongoing research, the question of how, and formally also whether, SGK1 acts on the epithelial sodium channel should be resolved in the near future.
Loffing
J
J
Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Summa
V
V
Zecevic
M
M
Verrey
F
F
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D007686:Kidney Tubules, Distal / Q000502:physiology*; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases