Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption

Phosphoinositide S-kinase is required for aldosterone-regulated sodium reab sorption. Am. J. Physiol. 277 (Cell Physiol. 46): C531-C536, 1999.-Aldoster one, a steroid hormone, regulates renal Nat reabsorption and, therefore, pl ays an important role in the maintenance of salt and water balance. In a mo del renal epithelial cell line (A6) we have found that phosphoinositide S-k inase (PI 3-kinase) activity is required for aldosterone-stimulated Na+ rea bsorption. Inhibition of PI 3-kinase by the specific inhibitor LY-294002 ma rkedly reduces both basal and aldosterone-stimulated Nat transport. Further , one of the products of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosph ate, is increased in response to aldosterone in intact A6 monolayers. This increase occurs just before the manifestation of the functional effect of t he hormone and is also inhibited by LY-294002. With the use of blocker-indu ced noise analysis, it has been demonstrated that inhibition of phosphoinos itide formation causes an inhibition of Na+ entry in both control and aldos terone-pretreated cultures by reducing the number of open functional epithe lial Na+ channels (ENaCs) in the apical membrane of the A6 cells. These nov el observations indicate that phosphoinositides are required for ENaC expre ssion and suggest a mechanism for aldosterone regulation of channel functio n.