Regulation of Cl- secretion by AMPK in vivo

Patthara Kongsuphol, Bernhard Hieke, Jiraporn Ousingsawat, Joana Almaca, Benoit Viollet, Rainer Schreiber, Karl Kunzelmann

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Previous in vitro studies suggested that Cl- currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the α1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl- secretion by AMPK in vivo. Using AMPKα1-/- mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl- secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKα1-/- and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl- conductance in basolaterally permeabilized colonic epithelium from AMPKα1+/+ but not AMPKα1 -/- mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl- secretion in epithelial tissues of AMPKα1-/- mice, but not in wild-type littermates. There was no effect on Ca 2+-mediated Cl- secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl- secretion was enhanced in the colon of AMPKα1-/- mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl- secretion mediated by CFTR is controlled by AMPK in vivo.

Original languageEnglish (US)
Pages (from-to)1071-1078
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume457
Issue number5
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Fingerprint

Adenylate Kinase
Adenosine Monophosphate
Phenformin
Phosphotransferases
Epithelium
Colon
Cystic Fibrosis Transmembrane Conductance Regulator
Physiological Stress
Wild Animals
Tissue
Protein-Serine-Threonine Kinases
Carbachol
Metabolism
Protein Isoforms
Adenosine Triphosphate
Animals

Keywords

  • AMPK
  • CFTR
  • Cystic fibrosis transmembrane conductance regulator

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Kongsuphol, P., Hieke, B., Ousingsawat, J., Almaca, J., Viollet, B., Schreiber, R., & Kunzelmann, K. (2009). Regulation of Cl- secretion by AMPK in vivo. Pflugers Archiv European Journal of Physiology, 457(5), 1071-1078. https://doi.org/10.1007/s00424-008-0577-3

Regulation of Cl- secretion by AMPK in vivo. / Kongsuphol, Patthara; Hieke, Bernhard; Ousingsawat, Jiraporn; Almaca, Joana; Viollet, Benoit; Schreiber, Rainer; Kunzelmann, Karl.

In: Pflugers Archiv European Journal of Physiology, Vol. 457, No. 5, 01.03.2009, p. 1071-1078.

Research output: Contribution to journalArticle

Kongsuphol, P, Hieke, B, Ousingsawat, J, Almaca, J, Viollet, B, Schreiber, R & Kunzelmann, K 2009, 'Regulation of Cl- secretion by AMPK in vivo', Pflugers Archiv European Journal of Physiology, vol. 457, no. 5, pp. 1071-1078. https://doi.org/10.1007/s00424-008-0577-3
Kongsuphol P, Hieke B, Ousingsawat J, Almaca J, Viollet B, Schreiber R et al. Regulation of Cl- secretion by AMPK in vivo. Pflugers Archiv European Journal of Physiology. 2009 Mar 1;457(5):1071-1078. https://doi.org/10.1007/s00424-008-0577-3
Kongsuphol, Patthara ; Hieke, Bernhard ; Ousingsawat, Jiraporn ; Almaca, Joana ; Viollet, Benoit ; Schreiber, Rainer ; Kunzelmann, Karl. / Regulation of Cl- secretion by AMPK in vivo. In: Pflugers Archiv European Journal of Physiology. 2009 ; Vol. 457, No. 5. pp. 1071-1078.
@article{a4cdacca68404a56a5975b499148225b,
title = "Regulation of Cl- secretion by AMPK in vivo",
abstract = "Previous in vitro studies suggested that Cl- currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the α1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl- secretion by AMPK in vivo. Using AMPKα1-/- mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl- secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKα1-/- and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl- conductance in basolaterally permeabilized colonic epithelium from AMPKα1+/+ but not AMPKα1 -/- mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl- secretion in epithelial tissues of AMPKα1-/- mice, but not in wild-type littermates. There was no effect on Ca 2+-mediated Cl- secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl- secretion was enhanced in the colon of AMPKα1-/- mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl- secretion mediated by CFTR is controlled by AMPK in vivo.",
keywords = "AMPK, CFTR, Cystic fibrosis transmembrane conductance regulator",
author = "Patthara Kongsuphol and Bernhard Hieke and Jiraporn Ousingsawat and Joana Almaca and Benoit Viollet and Rainer Schreiber and Karl Kunzelmann",
year = "2009",
month = "3",
day = "1",
doi = "10.1007/s00424-008-0577-3",
language = "English (US)",
volume = "457",
pages = "1071--1078",
journal = "Pflugers Archiv European Journal of Physiology",
issn = "0031-6768",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Regulation of Cl- secretion by AMPK in vivo

AU - Kongsuphol, Patthara

AU - Hieke, Bernhard

AU - Ousingsawat, Jiraporn

AU - Almaca, Joana

AU - Viollet, Benoit

AU - Schreiber, Rainer

AU - Kunzelmann, Karl

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Previous in vitro studies suggested that Cl- currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the α1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl- secretion by AMPK in vivo. Using AMPKα1-/- mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl- secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKα1-/- and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl- conductance in basolaterally permeabilized colonic epithelium from AMPKα1+/+ but not AMPKα1 -/- mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl- secretion in epithelial tissues of AMPKα1-/- mice, but not in wild-type littermates. There was no effect on Ca 2+-mediated Cl- secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl- secretion was enhanced in the colon of AMPKα1-/- mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl- secretion mediated by CFTR is controlled by AMPK in vivo.

AB - Previous in vitro studies suggested that Cl- currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the α1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl- secretion by AMPK in vivo. Using AMPKα1-/- mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl- secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKα1-/- and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl- conductance in basolaterally permeabilized colonic epithelium from AMPKα1+/+ but not AMPKα1 -/- mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl- secretion in epithelial tissues of AMPKα1-/- mice, but not in wild-type littermates. There was no effect on Ca 2+-mediated Cl- secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl- secretion was enhanced in the colon of AMPKα1-/- mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl- secretion mediated by CFTR is controlled by AMPK in vivo.

KW - AMPK

KW - CFTR

KW - Cystic fibrosis transmembrane conductance regulator

UR - http://www.scopus.com/inward/record.url?scp=59849102624&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59849102624&partnerID=8YFLogxK

U2 - 10.1007/s00424-008-0577-3

DO - 10.1007/s00424-008-0577-3

M3 - Article

C2 - 18752001

AN - SCOPUS:59849102624

VL - 457

SP - 1071

EP - 1078

JO - Pflugers Archiv European Journal of Physiology

JF - Pflugers Archiv European Journal of Physiology

SN - 0031-6768

IS - 5

ER -