Role of Sgk1 in salt and potassium homeostasis.
Aldosterone plays a pivotal role in NaCl and K(+) homeostasis by stimulation of Na(+) reabsorption and K(+) secretion in the aldosterone-sensitive distal nephron (ASDN). Recent studies demonstrated that the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by aldosterone in the ASDN and that polymorphisms of the kinase associate with arterial blood pressure in normotensive subjects. This review discusses the role of Sgk1 in NaCl and K(+) homeostasis as evidenced by in vivo studies, including those in Sgk1-deficient mice. The studies indicate that Sgk1 is not absolutely required for Na(+) reabsorption and K(+) secretion in the ASDN. On a standard NaCl and K(+) diet, modestly enhanced plasma aldosterone concentrations appear sufficient to establish a compensated phenotype in the absence of Sgk1. The kinase is necessary, however, for upregulation of transcellular Na(+) reabsorption in the ASDN. This may involve Sgk1-mediated stimulation of basolateral Na(+)-K(+)-ATPase as well as retention of epithelial Na(+) channel, ENaC, in the apical membrane. Such an upregulation is a prerequisite for adequate adaptation of 1) renal NaCl reabsorption during restricted dietary NaCl intake, as well as 2) K(+) secretion in response to enhanced K(+) intake. Thus gain-of-function mutations of Sgk1 are expected to result in renal NaCl retention and enhanced K(+) secretion. Further studies are required to elucidate renal and nonrenal aldosterone-induced effects of Sgk1, the role of other Sgk1 activators, as well as the link of Sgk1 polymorphisms to arterial hypertension in humans.
Vallon
Volker
V
Department of Medicine, University. of California San Diego and Veterans Affairs Medical Center, 3350 La Jolla Village Drive (9151 San Diego, CA 92161, USA. vvallon@ucsd.edu
Wulff
Peer
P
Huang
Dan Yang
DY
Loffing
Johannes
J
Völkl
Harald
H
Kuhl
Dietmar
D
Lang
Florian
F
D000450:Aldosterone / Q000502:physiology; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D015870:Gene Expression; D005838:Genotype; D006706:Homeostasis; D017874:Immediate-Early Proteins; D007668:Kidney / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D010641:Phenotype; D011188:Potassium / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D011188:Potassium; D017346:Protein Serine-Threonine Kinases; D012965:Sodium Chloride; D000099184:Serum-Glucocorticoid Regulated Kinases