HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/3/C717    most recent 00006.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Helms, M. N. Articles by Eaton, D. C. Search for Related Content PubMed PubMed Citation Articles by Helms, M. N. Articles by Eaton, D. C.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Role of SGK1 in nitric oxide inhibition of ENaC in Na⁺-transporting epithelia

¹Department of Physiology, Emory University School of Medicine; and ²Department of Medicine, Atlanta Veterans Affairs Medical Center and Emory University Medical Center, Atlanta, Georgia

Submitted 6 January 2005 ; accepted in final form 12 April 2005

Several studies have shown that nitric oxide (NO) inhibits Na⁺ transport in renal and alveolar monolayers. However, the mechanisms by which NO alters epithelial Na⁺ channel (ENaC) activity is unclear. Therefore, we examined the effect of applying the NO donor drug L-propanamine 3,2-hydroxy-2-nitroso-1-propylhidrazino (PAPA-NONOate) to cultured renal epithelial cells. A6 and M1 cells were maintained on permeable supports in medium containing 1.5 µM dexamethasone and 10% bovine serum. After 1.5 µM PAPA-NONOate was applied, amiloride-sensitive short-circuit current measurements decreased 29% in A6 cells and 44% in M1 cells. This differed significantly from the 3% and 19% decreases in A6 and M1 cells, respectively, treated with control donor compound (P < 0.0005). Subsequent application of PAPA-NONOate to amiloride-treated control (no NONOate) A6 and M1 cells did not further decrease transepithelial current. In single-channel patch-clamp studies, NONOate significantly decreased ENaC open probability (P_o) from 0.186 ± 0.043 to 0.045 ± 0.009 (n = 7; P < 0.05) without changing the unitary current. We also showed that aldosterone significantly decreased NO production in primary cultures of alveolar type II (ATII) epithelial cells. Because inducible nitric oxide synthase (iNOS) coimmunoprecipitated with the serum- and glucocorticoid-inducible kinase (SGK1) and both proteins colocalized in the cytoplasm (as shown in our studies in mouse ATII cells), SGK1 may also be important in regulating NO production in the alveolar epithelium. Our study also identified iNOS as a novel SGK1 phosphorylated protein (at S733 and S903 residues in miNOS) suggesting that one way in which SGK1 could increase Na⁺ transport is by altering iNOS production of NO.

aldosterone; epithelial sodium channel; serum- and glycocorticoid-inducible kinase

This article has been cited by other articles:

				L. Yu, H.-F. Bao, J. L. Self, D. C. Eaton, and M. N. Helms Aldosterone-induced increases in superoxide production counters nitric oxide inhibition of epithelial Na channel activity in A6 distal nephron cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1666 - F1677. [Abstract] [Full Text] [PDF]

				W. Song and S. Matalon Modulation of alveolar fluid clearance by reactive oxygen-nitrogen intermediates Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L855 - L858. [Full Text] [PDF]

				T. Li, S. Koshy, and H. G. Folkesson Involvement of {alpha}ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1069 - L1078. [Abstract] [Full Text] [PDF]

				T. Slowinski, P. Kalk, M. Christian, F. Schmager, K. Relle, M. Godes, H. Funke-Kaiser, H.-H. Neumayer, C. Bauer, F. Theuring, et al. Cell-type specific interaction of endothelin and the nitric oxide system: pattern of prepro-ET-1 expression in kidneys of L-NAME treated prepro-ET-1 promoter-lacZ-transgenic mice J. Physiol., June 15, 2007; 581(3): 1173 - 1181. [Abstract] [Full Text] [PDF]

				K. Sobczak, A. Willing, K. Kusche, N. Bangel, and W.-M. Weber Amiloride-sensitive sodium absorption is different in vertebrates and invertebrates Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2318 - R2327. [Abstract] [Full Text] [PDF]

				R. R. Quesnell, X. Han, and B. D. Schultz Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1739 - C1745. [Abstract] [Full Text] [PDF]

				F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Physiol Rev, October 1, 2006; 86(4): 1151 - 1178. [Abstract] [Full Text] [PDF]