Aldosterone Regulation of Protein Kinase Signaling Pathways and Renal Na+ Transport by Non-genomic Mechanisms
Aldosterone is the key regulating hormone of whole-body fluid and electrolyte homeostasis. Perturbations in aldosterone synthesis and over-activation of the mineralocorticoid receptor (MR) can lead to excess salt reabsorption and hypertension. The cortical collecting duct (CCD) is the main site of action in the kidney for aldosterone regulation of whole-body sodium homeostasis through actions on the epithelial sodium channel (ENaC) and the Na/K-ATPase (Na/K pump). Aldosterone stimulates ENaC trafficking into the apical cell membranes in the CCD and enhances channel stability and open probability, as well as activating the basolateral membrane Na/K pump to produce an overall increase in the transepithelial reabsorption of sodium. Aldosterone/MR regulates the activity of ENaC in the CCD through both rapid non-genomic (secs-mins) and latent genomic (hours-days) signaling pathways. These rapid and slow responses of renal Na+ transport pathways to aldosterone are often treated as distinct and separate events. However, recent evidence points to a close integration between genomic and non-genomic responses to aldosterone to regulate ENaC and Na/K pump activity via protein kinase signaling pathways. Here, we review the integration of aldosterone membrane-initiated non-genomic and nuclear genomic regulations of renal sodium transport via protein kinase signaling pathways and in particular via protein kinase D isoforms.
CommentsThe original book chapter is available at https://www.intechopen.com/ Editor: Prof Brian Harvey, Molecular Medicine, RCSI Part of the ‘Aldosterone-Mineralocorticoid Receptor: Cell Biology to Translational Medicine’ collection: https://repository.rcsi.com/account/home#/collections/4974911
Published CitationThomas W, Harevy B. Aldosterone Regulation of Protein Kinase Signaling Pathways and Renal Na+ Transport by Non-genomic Mechanisms In: Harvey B, Jaisser F, editors. Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine: InTechOpen; 2019.
- Molecular Medicine