Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption.
Aldosterone, 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.
Blazer-Yost
B L
BL
Biology Department, Indiana University, Purdue University at Indianapolis, Indianapolis 46202, Indiana, USA. bblazer@iupui.edu
Păunescu
T G
TG
Helman
S I
SI
Lee
K D
KD
Vlahos
C J
CJ
D000042:Absorption; D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053503:Epithelial Sodium Channels; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism
D000450:Aldosterone; D002867:Chromones; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012964:Sodium; D015222:Sodium Channels; C060974:phosphatidylinositol 3,4,5-triphosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one