Difference in regulation mechanisms of ENaC by aldosterone and glucocorticords
Chengchun Tang, Hao Zhang, Su Wang, Juyou Wu, Yuchun Gu, Jeng Wei
.
DOI: 10.4236/health.2009.13025   PDF    HTML     5,266 Downloads   9,290 Views   Citations

Abstract

Na+ transport occurs across many epithelial surfaces and plays a key role in regulating salt and water absorption. The molecular pathway underlying this Na+ transport is the epithelial Na channel (ENaC), which is strictly determined by a variety of hormones like aldosterone, ADH and glucocorticoids. In this study, we found that stimulation of either aldosterone or dexameth- asone (Dex) distributed ENaC channel on the apical membrane of mouse cortical collecting duct cells (M1). In the single channel recordings from excised membrane, high density ENaC was found in the cell with a dome shape by the treatment of either dex or aldosterone. However, low active ENaC was revealed in intact cells treated with dex, when compared to cells treated with aldosterone. Only 5.84% of cells treated with dex containing ENaC exhibited ENaC current transition in the cell-attach recording, whereas 40% of cells treated with aldosterone containing ENaC exhibited ENaC current transition. ENaC currents appeared rapid rundown within 5 min-utes since formation of inside-out configuration in cells treated with aldosterone but not with dex. SKF-525A, a general antagonist of CYP, failed to significantly enhance ENaC activity in intact cells treated with dex, but EGTA, which deforming the cells, increased the ENaC activity in the cells treated with dex. PTX, an antagonist of G-protein, reversed the effect of aldosterone on number of active ENaC in intact cells. Based on our obser-vation, we concluded that there are different mechanisms in regulation of ENaC activity be-tween stimulation of aldosterone and glucocor-ticoids. The activation of G-protein is required to maintain the activity of ENaC in the collecting ducts.

Share and Cite:

Tang, C. , Zhang, H. , Wang, S. , Wu, J. , Gu, Y. and Wei, J. (2009) Difference in regulation mechanisms of ENaC by aldosterone and glucocorticords. Health, 1, 152-158. doi: 10.4236/health.2009.13025.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Y. Guan, C. Hao, D. R. Cha, R. Rao, W. Lu, D. E. Kohan, M. A. Magnuson, R. Redha, Y. Zhang, M. D. Breyer, (2005) Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated re-nal salt absorption. Nat Med, 11, 861-866.
[2] P. Factor, G. M. Mutlu, L. Chen, J. Mohameed, A. T. Akhmedov, F. J. Meng, T. Jilling, E. R. Lewis, M. D. Johnson, A. Xu, D. Kass, J. M. Martino, A. Bellmeyer, J. S. Albazi, C. Emala, H. T. Lee, L. G. Dobbs, S. Matalon, (2007) Adenosine regulation of alveolar fluid clearance. Proc Natl Acad Sci U S A, 104, 4083-4088.
[3] J. D. Stockand, (2002) New ideas about aldosterone sig-naling in epithelia. Am J Physiol Renal Physiol, 282, F559-576.
[4] C. Boyd, A. Naray-Fejes-Toth, (2005) Gene regulation of ENaC subunits by serum- and glucocorticoid-inducible kinase-1. Am J Physiol Renal Physiol, 288, F505-512.
[5] J. Wang, P. Barbry, A. C. Maiyar, D. J. Rozansky, A. Bhargava, M. Leong, G. L. Firestone, D. Pearce, (2001) SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport. Am J Physiol Renal Physiol, 280, F303-313.
[6] P. MacDonald, S. MacKenzie, L. E. Ramage, J. R. Seckl, R. W. Brown, (2000) Corticosteroid regulation of amilo-ride-sensitive sodium-channel subunit mRNA expression in mouse kidney. J Endocrinol, 165, 25-37.
[7] O. A. Itani, S. D. Auerbach, R. F. Husted, K. A. Volk, S. Ageloff, M. A. Knepper, J. B. Stokes, C. P. Thomas, (2002a) Glucocorticoid-stimulated lung epithelial Na(+) transport is associated with regulated ENaC and sgk1 ex-pression. Am J Physiol Lung Cell Mol Physiol, 282, L631-641.
[8] O. A. Itani, K. Z. Liu, K. L. Cornish, J. R. Campbell, C. P. Thomas, (2002b) Glucocorticoids stimulate human sgk1 gene expression by activation of a GRE in its 5'-flanking region. Am J Physiol Endocrinol Metab, 283, E971-979.
[9] K. Nakamura, J. B. Stokes, P. B. McCray Jr, (2002) En-dogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am J Physiol Cell Physiol, 283, C762-772.
[10] S. R. Pondugula, J. D. Sanneman, P. Wangemann, P. G. Milhaud, D. C. Marcus, (2004) Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel. Am J Physiol Renal Physiol, 286, F1127-1135.
[11] V. Shlyonsky, A. Goolaerts, R. Van Beneden, S. Sari-ban-Sohraby, (2005) Differentiation of epithelial Na+ channel function: An in vitro model. J Biol Chem, 280, 24181-24187.
[12] S. R. Pondugula, N. N. Raveendran, Z. Ergonul, Y. Deng, J Chen, J. D. Sanneman, L. G. Palmer, D. C. Marcus, (2006) Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithe-lium of neonatal rat. Physiol Genomics, 24, 114-123.
[13] R. R. Quesnell, X. Han, B. D. Schultz, (2007) Glucocor-ticoids stimulate ENaC upregulation in bovine mammary epithelium. Am J Physiol Cell Physiol.
[14] M. Horster, (2000) Embryonic epithelial membrane trans-porters. Am J Physiol Renal Physiol, 279, F982-996.
[15] M. T. Bens, V. Vallet, F. Cluzeaud, L. Pascual-Letallec, A. Kahn, M. E. Rafestin-Oblin, B. C. Rossier, A. Vandewalle, (1999) Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line. J Am Soc Nephrol, 10, 923-934.
[16] H. R. Kaslow, L. K. Lim, J. Moss, D. D. Lesikar, (1987) Structure-activity analysis of the activation of pertussis toxin. Biochemistry, 26, 123-127.
[17] J. Gorelik, Y. Zhang, D. Sanchez, A. Shevchuk, G. Frolenkov, M. Lab, D. Klenerman, C. Edwards, Y. Kor-chev, (2005) Aldosterone acts via an ATP autocrine/ paracrine system: the Edelman ATP hypothesis revisited. Proc Natl Acad Sci U S A, 102, 15000-15005.
[18] H. P. Ma, S. Saxena, D. G. Warnock, (2002b) Anionic phospholipids regulate native and expressed epithelial sodium channel (ENaC). J Biol Chem, 277, 7641-7644.
[19] G. Yue, B. Malik, G. Yue, D. C. Eaton, (2002) Phosphati-dylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells. J. Biol Chem, 277, 11965-11969.
[20] Y. Wei, D. H. Lin, R. Kemp, G. S. Yaddanapudi, A. Nas-jletti, J. R. Falck, W. H. Wang, (2004) Arachidonic acid inhibits epithelial Na channel via cytochrome P450 (CYP) epoxygenase-dependent metabolic pathways. J Gen Physiol, 124, 719-727.
[21] Y. Wei, P. Sun, Z. Wang, B. Yang, M. A. Carroll, W. H. Wang, (2006) Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid. Am J Physiol Renal Physiol, 290, F1163-1168.
[22] Q. Tong, J. D. Stockand, (2005) Receptor tyrosine kinases mediate epithelial Na(+) channel inhibition by epidermal growth factor. Am J Physiol Renal Physiol, 288, F150- 161.
[23] D. W. Hilgemann, S. Feng, C. Nasuhoglu, (2001) The complex and intriguing lives of PIP2 with ion channels and transporters. Sci STKE, RE19.
[24] M. N. Helms, L. Liu, Y. Y. Liang, O. Al-Khalili, A. Vandewalle, S. Saxena, D. C. Eaton, H. P. Ma, (2005) Phosphatidylinositol 3,4,5-trisphosphate mediates aldos-terone stimulation of epithelial sodium channel (ENaC) and interacts with gamma-ENaC. J Biol Chem, 280, 40885-40891.
[25] H. P. Ma, D. C. Eaton, (2005) Acute regulation of epithe-lial sodium channel by anionic phospholipids. J Am Soc Nephrol, 16, 3182-3187.
[26] O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, J. D. Stockand, (2007) Molecu lar determinants of PI(4,5)P2 and PI(3,4,5)P3 regulation of the epithelial Na+ channel. J Gen Physiol, 130, 399-413.
[27] K. M. Weixel, R. S. Edinger, L. Kester, C. J. Guerriero, H. Wang, L. Fang, T. R. Kleyman, P. A. Welling, O. A. Weisz, J. P. Johnson, (2007) Phosphatidylinositol 4-phosphate 5-kinase reduces cell surface expression of the epithelial sodium channel (ENaC) in cultured collecting duct cells. J. Biol Chem.
[28] Q. Tong, N. Gamper, J. L. Medina, M. S. Shapiro, J. D. Stockand, (2004b) Direct activation of the epithelial Na(+) channel by phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate produced by phos-phoinositide 3-OH kinase. J Biol Chem, 279, 22654- 22663.
[29] O. Pochynyuk, Q. Tong, J. Medina, A. Vandewalle, A. Staruschenko, V. Bugaj, J. D. Stockand, (2007) Molecu lar determinants of PI(4,5)P2 and PI(3,4,5)P3 regulation of the epithelial Na+ channel. J Gen Physiol, 130, 399-413.
[30] R. L. Doughman, A. J Firestone, R. A. Anderson, (2003) Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place. J Membr Biol, 194, 77-89.
[31] P. A. Oude Weernink, M. Schmidt, K. H. Jakobs, (2004) Regulation and cellular roles of phosphoinositide 5- kinases. Eur J Pharmacol, 500, 87-99.
[32] A. Staruschenko, O. M. Pochynyuk, Q. Tong, J. D. Stockand, (2005) Ras couples phosphoinositide 3-OH kinase to the epithelial Na+ channel. Biochim Biophys Acta, 1669, 108-115.
[33] K. Kunzelmann, T. Bachhuber, R. Regeer, D. Markovich, J. Sun, R. Schreiber, (2005) Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2. Faseb J, 19, 142-143.
[34] T. Rohacs, J. Chen, G. D. Prestwich, D. E. Logothetis, (1999) Distinct specificities of inwardly rectifying K(+) channels for phosphoinositides. J Biol Chem, 274, 36065- 36072.
[35] R. C. Hardie, (2003a) Regulation of TRP channels via lipid second messengers. Annu Rev Physiol, 65, 735-759.
[36] H. P. Ma, L. Li, Z. H. Zhou, D. C. Eaton, D. G. Warnock, (2002a) ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells. Am J Physiol Renal Physiol, 282, F501-505.
[37] O. Pochynyuk, A. Staruschenko, Q. Tong, J. Medina, J. D. Stockand, (2005) Identification of a functional phos-phatidylinositol 3,4,5-trisphosphate binding site in the epithelial Na+ channel. J Biol Chem, 280, 37565-37571.
[38] R. C. Hardie, (2003b) TRP channels in Drosophila photore-ceptors: the lipid connection. Cell Calcium, 33, 385- 393.
[39] R. C. Hardie, (2004) Regulation of Drosophila TRP channels by lipid messengers. Novartis Found Symp, 258, 160-167; discussion 167-171, 263-166.
[40] D. Pearce, (2003) SGK1 regulation of epithelial sodium transport. Cell Physiol Biochem, 13, 13-20.
[41] Q. Tong, R. E. Booth, R. T. Worrell, J. D. Stockand, (2004a) Regulation of Na+ transport by aldosterone: sig-naling convergence and cross talk between the PI3-K and MAPK1/2 cascades. Am J Physiol Renal Physiol, 286, F1232-1238.
[42] L. Gambling, R. E. Olver, G. K. Fyfe, P. J. Kemp, D. L. Baines, (1998) Differential regulation of Na+ and Cl- conductances by PTX-sensitive G proteins in fetal lung apical membrane vesicles. Biochim Biophys Acta, 1372, 187-197.
[43] B. K. Berdiev, A. G. Prat, H. F. Cantiello, D. A. Ausiello, C. M. Fuller, B. Jovov, D. J Benos, I. I. Ismailov, (1996) Regulation of epithelial sodium channels by short actin filaments. J Biol Chem, 271, 17704-17710.
[44] J. B. Zuckerman, X. Chen, J. D. Jacobs, B. Hu, T. R. Kleyman, P. R. Smith, (1999) Association of the epithelial sodium channel with Apx and alpha-spectrin in A6 renal epithelial cells. J Biol Chem, 274, 23286-23295.
[45] C. Mazzochi, J. K. Bubien, P. R. Smith, D. J. Benos, (2006) The carboxyl terminus of the alpha-subunit of the amilo-ride-sensitive epithelial sodium channel binds to F-actin. J Biol Chem, 281, 6528-6538.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.