Expression of the epithelial Na+ channel and other components of an aldosterone response pathway in human adrenocortical cells

Timothy J. Burton, Georgina Cope, Jing Wang, Joalice C. Sim, Azizan Elena Aisha, Kevin M. O'Shaughnessy, Morris J. Brown

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have unexpectedly found expression of the epithelial Na+ channel (ENaC) in human adrenocortical cells and tested the hypothesis that these cells contain the components of an aldosterone response pathway. Tissue was obtained from patients undergoing adrenalectomy and mRNA and protein expression of recognised components of an aldosterone-response pathway were determined by RT-PCR and Western blotting. The effects of mineralocorticoid receptor agonists and antagonists, amiloride analogues, and extracellular Na+ on basal and stimulated aldosterone release from immortalised (H295R) cells were determined by radioimmunoassay. Expression of mRNA for α-, β- and γ-subunits of ENaC, the mineralocorticoid receptor, Nedd4L, Sgk1 and 11β hydroxysteroid dehydrogenase type II was confirmed in human adrenal cortex. Using Western blotting α-, β- and γ-ENaC expression was demonstrated in adrenocortical cells. Measurements of 24 h aldosterone release from H295R cells showed stimulation by K+ and angiotensin II, suppression by both Na+ and high-concentration 5-(N-ethyl-N-isopropyl) amiloride (EIPA, blocker of Na+-H+ exchange) and no change with benzamil (ENaC blocker). 22Na-uptake into H295R cells was inhibited by EIPA, but not by benzamil. Our experiments suggest that the components of an aldosterone response pathway are present in human adrenal cortex. Studies in H295R cells, however, suggest that ENaC is not an important mediator of 22Na-uptake or aldosterone production. Further studies are required to determine the importance of an adrenal aldosterone response pathway.

Original languageEnglish
Pages (from-to)176-181
Number of pages6
JournalEuropean Journal of Pharmacology
Volume613
Issue number1-3
DOIs
Publication statusPublished - 24 Jun 2009
Externally publishedYes

Fingerprint

Epithelial Sodium Channels
Aldosterone
Adrenal Cortex
Western Blotting
11-beta-Hydroxysteroid Dehydrogenases
Mineralocorticoid Receptor Antagonists
Mineralocorticoid Receptors
Messenger RNA
Amiloride
Adrenalectomy
Cellular Structures
Angiotensin II
Radioimmunoassay
Polymerase Chain Reaction

Keywords

  • Adrenal cortex
  • Aldosterone
  • Epithelial Na channel

ASJC Scopus subject areas

  • Pharmacology

Cite this

Expression of the epithelial Na+ channel and other components of an aldosterone response pathway in human adrenocortical cells. / Burton, Timothy J.; Cope, Georgina; Wang, Jing; Sim, Joalice C.; Elena Aisha, Azizan; O'Shaughnessy, Kevin M.; Brown, Morris J.

In: European Journal of Pharmacology, Vol. 613, No. 1-3, 24.06.2009, p. 176-181.

Research output: Contribution to journalArticle

Burton, Timothy J. ; Cope, Georgina ; Wang, Jing ; Sim, Joalice C. ; Elena Aisha, Azizan ; O'Shaughnessy, Kevin M. ; Brown, Morris J. / Expression of the epithelial Na+ channel and other components of an aldosterone response pathway in human adrenocortical cells. In: European Journal of Pharmacology. 2009 ; Vol. 613, No. 1-3. pp. 176-181.
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