SGK1-dependent salt appetite in pregnant mice.

AIM: Pregnancy is typically paralleled by substantial increase in maternal extracellular fluid volume, requiring net accumulation of water and NaCl. The positive water and salt balance is accomplished at least in part by increased uptake of salt secondary to enhanced salt appetite. Little is known about the underlying cellular mechanisms. Stimulation of salt appetite by mineralocorticoids, however, is known to be dependent on the serum- and glucocorticoid-inducible kinase SGK1. METHODS: To test for a role of SGK1 in the stimulation of salt appetite during pregnancy, fluid intake was recorded in pregnant SGK1 knockout mice (sgk1(-/-) ) and their wild type littermates (sgk1(+/+) ). The mice were offered two bottles, one with plain water and the other with isotonic saline. RESULTS: In early pregnancy, i.e. up to 10 days prior to parturition, the sgk1(+/+) mice displayed a significant preference for saline, whereas the sgk1(-/-) mice preferred water. Accordingly, the water intake was significantly smaller and saline intake was significantly larger in sgk1(+/+) mice than in sgk1(-/-) mice and the preference for water was significantly stronger in sgk1(-/-) mice than in sgk1(+/+) mice. Plasma aldosterone levels were higher in sgk1(-/-) mice than in sgk1(+/+) mice, a difference contrasting the enhanced salt appetite of sgk1(+/+) mice. CONCLUSIONS: SGK1 participates in the stimulation of salt appetite during pregnancy.

Akt2/PKBbeta-sensitive regulation of renal phosphate transport.

AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles. RESULTS: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice. CONCLUSIONS: Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.