Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption
1999; American Physical Society; Volume: 277; Issue: 3 Linguagem: Inglês
10.1152/ajpcell.1999.277.3.c531
ISSN1522-1563
AutoresBonnie L. Blazer‐Yost, Teodor G. Păunescu, S. I. Helman, Kimberly D. Lee, Chris J. Vlahos,
Tópico(s)Electrolyte and hormonal disorders
ResumoAldosterone, a steroid hormone, regulates renal Na + reabsorption and, therefore, plays an important role in the maintenance of salt and water balance. In a model renal epithelial cell line (A6) we have found that phosphoinositide 3-kinase (PI 3-kinase) activity is required for aldosterone-stimulated Na + reabsorption. Inhibition of PI 3-kinase by the specific inhibitor LY-294002 markedly reduces both basal and aldosterone-stimulated Na + transport. Further, one of the products of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosphate, is increased in response to aldosterone in intact A6 monolayers. This increase occurs just before the manifestation of the functional effect of the hormone and is also inhibited by LY-294002. With the use of blocker-induced noise analysis, it has been demonstrated that inhibition of phosphoinositide formation causes an inhibition of Na + entry in both control and aldosterone-pretreated cultures by reducing the number of open functional epithelial Na + channels (ENaCs) in the apical membrane of the A6 cells. These novel observations indicate that phosphoinositides are required for ENaC expression and suggest a mechanism for aldosterone regulation of channel function.
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