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Epithelial Na⁺ channel activity in human airway epithelial cells

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Epithelial Na⁺ channel activity in human airway epithelial cells : the role of serum and glucocorticoid-inducible kinase 1. / Watt, Gordon B.; Ismail, Noor A. S.; Caballero, Agustin Garcia; Land, Stephen C.; Wilson, Stuart M.

In: British Journal of Pharmacology, Vol. 166, No. 4, 06.2012, p. 1272-1289.

Research output: Contribution to journalArticle

Harvard

Watt, GB, Ismail, NAS, Caballero, AG, Land, SC & Wilson, SM 2012, 'Epithelial Na⁺ channel activity in human airway epithelial cells: the role of serum and glucocorticoid-inducible kinase 1' British Journal of Pharmacology, vol 166, no. 4, pp. 1272-1289.

APA

Watt, G. B., Ismail, N. A. S., Caballero, A. G., Land, S. C., & Wilson, S. M. (2012). Epithelial Na⁺ channel activity in human airway epithelial cells: the role of serum and glucocorticoid-inducible kinase 1. British Journal of Pharmacology, 166(4), 1272-1289doi: 10.1111/j.1476-5381.2012.01860.x

Vancouver

Watt GB, Ismail NAS, Caballero AG, Land SC, Wilson SM. Epithelial Na⁺ channel activity in human airway epithelial cells: the role of serum and glucocorticoid-inducible kinase 1. British Journal of Pharmacology. 2012 Jun;166(4):1272-1289.

Author

Watt, Gordon B.; Ismail, Noor A. S.; Caballero, Agustin Garcia; Land, Stephen C.; Wilson, Stuart M. / Epithelial Na⁺ channel activity in human airway epithelial cells : the role of serum and glucocorticoid-inducible kinase 1.

In: British Journal of Pharmacology, Vol. 166, No. 4, 06.2012, p. 1272-1289.

Research output: Contribution to journalArticle

Bibtex - Download

@article{416075675a0342beb04957b6ccb65951,
title = "Epithelial Na⁺ channel activity in human airway epithelial cells",
author = "Watt, {Gordon B.} and Ismail, {Noor A. S.} and Caballero, {Agustin Garcia} and Land, {Stephen C.} and Wilson, {Stuart M.}",
note = "© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.",
year = "2012",
volume = "166",
number = "4",
pages = "1272--1289",
journal = "British Journal of Pharmacology",
issn = "0007-1188",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Epithelial Na⁺ channel activity in human airway epithelial cells

T2 - the role of serum and glucocorticoid-inducible kinase 1

A1 - Watt,Gordon B.

A1 - Ismail,Noor A. S.

A1 - Caballero,Agustin Garcia

A1 - Land,Stephen C.

A1 - Wilson,Stuart M.

AU - Watt,Gordon B.

AU - Ismail,Noor A. S.

AU - Caballero,Agustin Garcia

AU - Land,Stephen C.

AU - Wilson,Stuart M.

PY - 2012/6

Y1 - 2012/6

N2 - <p>BACKGROUND AND PURPOSE Glucocorticoids appear to control control Na<sup>+</sup> absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelia Na<sup>+</sup> channel subunits (a-, ß- and y-ENaC). However, not all data support this model and the present study re-evaluates this hypothesis in order to clarify the mechanism that allows glucocorticoids to control ENaC activity. EXPERIMENTAL APPROACH Electrophysiological studies explored the effects of agents that suppress SGK1 activity upon glucocorticoid-induced ENaC activity in H441 human airway epithelial cells, whilst analyses of extracted proteins explored the associated changes to the activities of endogenous protein kinase substrates and the overall/surface expression of ENaC subunits. KEY RESULTS Although dexamethasone-induced (24 h) ENaC activity was dependent upon SGK1, prolonged exposure to this glucocorticoid did not cause sustained activation of this kinase and neither did it induce a coordinated increase in the surface abundance of a-, ß- and y-ENaC. Brief (3 h) exposure to dexamethasone, on the other hand, did not evoke Na<sup>+</sup> current but did activate SGK1 and cause SGK1-dependent increases in the surface abundance of a-, ß- and y-ENaC. CONCLUSIONS AND IMPLICATIONS Although glucocorticoids activated SGK1 and increased the surface abundance of a-, ß- and y-ENaC, these responses were transient and could not account for the sustained activation of ENaC. The maintenance of ENaC activity did, however, depend upon SGK1 and this protein kinase must therefore play an important but permissive role in glucocorticoid-induced ENaC activation. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.</p>

AB - <p>BACKGROUND AND PURPOSE Glucocorticoids appear to control control Na<sup>+</sup> absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelia Na<sup>+</sup> channel subunits (a-, ß- and y-ENaC). However, not all data support this model and the present study re-evaluates this hypothesis in order to clarify the mechanism that allows glucocorticoids to control ENaC activity. EXPERIMENTAL APPROACH Electrophysiological studies explored the effects of agents that suppress SGK1 activity upon glucocorticoid-induced ENaC activity in H441 human airway epithelial cells, whilst analyses of extracted proteins explored the associated changes to the activities of endogenous protein kinase substrates and the overall/surface expression of ENaC subunits. KEY RESULTS Although dexamethasone-induced (24 h) ENaC activity was dependent upon SGK1, prolonged exposure to this glucocorticoid did not cause sustained activation of this kinase and neither did it induce a coordinated increase in the surface abundance of a-, ß- and y-ENaC. Brief (3 h) exposure to dexamethasone, on the other hand, did not evoke Na<sup>+</sup> current but did activate SGK1 and cause SGK1-dependent increases in the surface abundance of a-, ß- and y-ENaC. CONCLUSIONS AND IMPLICATIONS Although glucocorticoids activated SGK1 and increased the surface abundance of a-, ß- and y-ENaC, these responses were transient and could not account for the sustained activation of ENaC. The maintenance of ENaC activity did, however, depend upon SGK1 and this protein kinase must therefore play an important but permissive role in glucocorticoid-induced ENaC activation. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.</p>

UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84861316702&md5=7c89f57bedcdd7e0b96b749c10329f03

U2 - 10.1111/j.1476-5381.2012.01860.x

DO - 10.1111/j.1476-5381.2012.01860.x

M1 - Article

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

VL - 166

SP - 1272

EP - 1289

ER -

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