Authors: Fuller, Peter J; Young, Morag J

Source: Expert Opinion on Therapeutic Targets, Volume 12, Number 3, March 2008 , pp. 377-382(6)

Publisher: Informa Healthcare

Abstract:

Background: Failure of sodium homeostasis contributes to a range of pathologies, particularly hypertension and cardiovascular disease but also respiratory diseases such as cystic fibrosis. As such the pathways involved in sodium homeostasis are now well recognised as important therapeutic targets. Objective: The 6th International Symposium on Aldosterone and ENaC explored recent developments in aldosterone synthesis and action, particularly with regard to its influence on the regulation of the epithelial sodium channel (ENaC). Methods: Although aldosterone biosynthesis, and indeed the mineralocorticoid receptor (MR), can be explored in isolation as can many aspects of the structure and function of the ENaC, the strength of the meeting was bringing these two topics together to explore the mechanisms of regulation of ENaC, including those mediated by activation of the MR. Results/conclusion: Given the number of individual presentations, any synthesis of the meeting will not do justice to all of the exciting work that was presented, however several themes emerged. The availability of crystal structures for the MR ligand-binding domain and a member of the ENaC family of channels have facilitated a number of structure function studies. The regulation of the activity of ENaC by the MR involves an interplay of factors which include transcriptional regulation, posttranslational modification and channel turnover. Several of these represent potential novel targets for the modulation of sodium homeostasis.

Keywords: amiloride; epithelial sodium channel; Liddle's syndrome; mineralocorticoid receptor; spironolactone

Document Type: Research article

DOI: http://dx.doi.org/10.1517/14728222.12.3.377

Affiliations: 1: Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia Tel: +61 3 9594 4395; Fax: +61 3 9594 6125;, Email: peter.fuller@princehenrys.org

Publication date: 2008-03-01

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