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Am J Physiol Renal Physiol 280: F675-F682, 2001;
0363-6127/01 $5.00
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Vol. 280, Issue 4, F675-F682, April 2001

Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK

Johannes Loffing2,*, Marija Zecevic1,*, Eric Féraille3, Brigitte Kaissling2, Carol Asher4, Bernard C. Rossier5, Gary L. Firestone6, David Pearce7, and François Verrey1

1 Institute of Physiology and 2 Institute of Anatomy, University of Zürich, CH-8057 Zürich; 3 Division de Néphrologie, Hôpital Cantonal Universitaire, CH-1211 Geneva; 4 Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel; 5 Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland; 6 Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of Califonia, Berkeley 94720; and 7 Division of Nephrology, Department of Medicine and Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California 94143

Aldosterone controls sodium reabsorption and potassium secretion in the aldosterone-sensitive distal nephron (ASDN). Although clearance measurements have shown that aldosterone induces these transports within 30-60 min, no early effects have been demonstrated in vivo at the level of the apical epithelial sodium channel (ENaC), the main effector of this regulation. Here we show by real-time RT-PCR and immunofluorescence that an aldosterone injection in adrenalectomized rats induces alpha -ENaC subunit expression along the entire ASDN within 2 h, whereas beta - and gamma -ENaC are constitutively expressed. In the proximal ASDN portions only, ENaC is shifted toward the apical cellular pole and the apical plasma membrane within 2 and 4 h, respectively. To address the question of whether the early aldosterone-induced serum and glucocorticoid-regulated kinase (SGK) might mediate this apical shift of ENaC, we analyzed SGK induction in vivo. Two hours after aldosterone, SGK was highly induced in all segment-specific cells of the ASDN, and its level decreased thereafter. In Xenopus laevis oocytes, SGK induced ENaC activation and surface expression by a kinase activity-dependent mechanism. In conclusion, the rapid in vivo accumulation of SGK and alpha -ENaC after aldosterone injection takes place along the entire ASDN, whereas the translocation of alpha ,beta ,gamma -ENaC to the apical plasma membrane is restricted to its proximal portions. Results from oocyte experiments suggest the hypothesis that a localized activation of SGK may play a role in the mediation of ENaC translocation.

Xenopus laevis oocytes; sodium transport; kidney; collecting duct; epithelial sodium channel; serum and glucocorticoid-regulated kinase


* J. Loffing and M. Zecevic contributed equally to this work.




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J. Physiol.Home page
D. A. de la Rosa, T. Coric, N. Todorovic, D. Shao, T. Wang, and C. M Canessa
Distribution and regulation of expression of serum- and glucocorticoid-induced kinase-1 in the rat kidney
J. Physiol., September 1, 2003; 551(2): 455 - 466.
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Am. J. Physiol. Renal Physiol.Home page
M. Auberson, N. Hoffmann-Pochon, A. Vandewalle, S. Kellenberger, and L. Schild
Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F459 - F471.
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Am. J. Physiol. Renal Physiol.Home page
J. Lebowitz, B. An, R. S. Edinger, M. L. Zeidel, and J. P. Johnson
Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F524 - F531.
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J. Am. Soc. Nephrol.Home page
O. G. Muller, R. G. Parnova, G. Centeno, B. C. Rossier, D. Firsov, and J.-D. Horisberger
Mineralocorticoid Effects in the Kidney: Correlation between {alpha}ENaC, GILZ, and Sgk-1 mRNA Expression and Urinary Excretion of Na+ and K+
J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1107 - 1115.
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J. Exp. Biol.Home page
M. Takada and M. Kasai
Prolactin increases open-channel density of epithelial Na+ channel in adult frog skin
J. Exp. Biol., April 15, 2003; 206(8): 1319 - 1323.
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Am. J. Physiol. Renal Physiol.Home page
J. Loffing and B. Kaissling
Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human
Am J Physiol Renal Physiol, April 1, 2003; 284(4): F628 - F643.
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Am. J. Physiol. Cell Physiol.Home page
D. Alvarez de la Rosa and C. M. Canessa
Role of SGK in hormonal regulation of epithelial sodium channel in A6 cells
Am J Physiol Cell Physiol, February 1, 2003; 284(2): C404 - C414.
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Am. J. Physiol. Renal Physiol.Home page
K. Y. Na, Y. K. Oh, J. S. Han, K. W. Joo, J. S. Lee, J.-H. Earm, M. A. Knepper, and G.-H. Kim
Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats
Am J Physiol Renal Physiol, January 1, 2003; 284(1): F133 - F143.
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J. Am. Soc. Nephrol.Home page
C. C. Yun, M. Palmada, H. M. Embark, O. Fedorenko, Y. Feng, G. Henke, I. Setiawan, C. Boehmer, E. J. Weinman, S. Sandrasagra, et al.
The Serum and Glucocorticoid-Inducible Kinase SGK1 and the Na+/H+ Exchange Regulating Factor NHERF2 Synergize to Stimulate the Renal Outer Medullary K+ Channel ROMK1
J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2823 - 2830.
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Biol. Reprod.Home page
M. Conti
Specificity of the Cyclic Adenosine 3',5'-Monophosphate Signal in Granulosa Cell Function
Biol Reprod, December 1, 2002; 67(6): 1653 - 1661.
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Am. J. Physiol. Endocrinol. Metab.Home page
O. A. Itani, K. Z. Liu, K. L. Cornish, J. R. Campbell, and C. P. Thomas
Glucocorticoids stimulate human sgk1 gene expression by activation of a GRE in its 5'-flanking region
Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E971 - E979.
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Am. J. Physiol. Renal Physiol.Home page
J. Nielsen, T.-H. Kwon, S. Masilamani, K. Beutler, H. Hager, S. Nielsen, and M. A. Knepper
Sodium transporter abundance profiling in kidney: effect of spironolactone
Am J Physiol Renal Physiol, November 1, 2002; 283(5): F923 - F933.
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Am. J. Physiol. Renal Physiol.Home page
E. Kamynina and O. Staub
Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na+ transport
Am J Physiol Renal Physiol, September 1, 2002; 283(3): F377 - F387.
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HypertensionHome page
A. Busjahn, A. Aydin, R. Uhlmann, C. Krasko, S. Bahring, T. Szelestei, Y. Feng, S. Dahm, A. M. Sharma, F. C. Luft, et al.
Serum- and Glucocorticoid-Regulated Kinase (SGK1) Gene and Blood Pressure
Hypertension, September 1, 2002; 40(3): 256 - 260.
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Am. J. Physiol. Renal Physiol.Home page
J. A. Schafer
Abnormal regulation of ENaC: syndromes of salt retention and salt wasting by the collecting duct
Am J Physiol Renal Physiol, August 1, 2002; 283(2): F221 - F235.
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Physiol. Rev.Home page
M. A. Matthay, H. G. Folkesson, and C. Clerici
Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema
Physiol Rev, July 1, 2002; 82(3): 569 - 600.
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Physiol. Rev.Home page
S. Kellenberger and L. Schild
Epithelial Sodium Channel/Degenerin Family of Ion Channels: A Variety of Functions for a Shared Structure
Physiol Rev, July 1, 2002; 82(3): 735 - 767.
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Am. J. Physiol. Renal Physiol.Home page
D. J. Rozansky, J. Wang, N. Doan, T. Purdy, T. Faulk, A. Bhargava, K. Dawson, and D. Pearce
Hypotonic induction of SGK1 and Na+ transport in A6 cells
Am J Physiol Renal Physiol, July 1, 2002; 283(1): F105 - F113.
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J. Am. Soc. Nephrol.Home page
H. L. Biner, M.-P. Arpin-Bott, J. Loffing, X. Wang, M. Knepper, S. C. Hebert, and B. Kaissling
Human Cortical Distal Nephron: Distribution of Electrolyte and Water Transport Pathways
J. Am. Soc. Nephrol., April 1, 2002; 13(4): 836 - 847.
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Am. J. Physiol. Renal Physiol.Home page
J. D. Stockand
New ideas about aldosterone signaling in epithelia
Am J Physiol Renal Physiol, April 1, 2002; 282(4): F559 - F576.
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J. Biol. Chem.Home page
H.-P. Ma, S. Saxena, and D. G. Warnock
Anionic Phospholipids Regulate Native and Expressed Epithelial Sodium Channel (ENaC)
J. Biol. Chem., March 1, 2002; 277(10): 7641 - 7644.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
J. B. Wade
Distribution of transporters along the mouse distal nephron: something old, something borrowed, something new
Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1019 - F1020.
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Am. J. Physiol. Renal Physiol.Home page
D. Rotin, V. Kanelis, and L. Schild
Trafficking and cell surface stability of ENaC
Am J Physiol Renal Physiol, September 1, 2001; 281(3): F391 - F399.
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Am. J. Physiol. Cell Physiol.Home page
C. J. Faletti, N. Perrotti, S. I. Taylor, and B. L. Blazer-Yost
sgk: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport
Am J Physiol Cell Physiol, March 1, 2002; 282(3): C494 - C500.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
J. Loffing, D. Loffing-Cueni, V. Valderrabano, L. Klausli, S. C. Hebert, B. C. Rossier, J. G. J. Hoenderop, R. J. M. Bindels, and B. Kaissling
Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron
Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1021 - F1027.
[Abstract] [Full Text] [PDF]




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