Epithelial Sodium Transport and Its Control by Aldosterone: The Story of Our Internal Environment Revisited

Abstract

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function

“…4, the DBD is highly conserved in vertebrate MRs, while the NTD and hinge domains are poorly conserved. The LBD has intermediate sequence conservation, which makes it useful for phylogenetic analysis of the MR , Rossier et al 2015. In addition, the sequence of the LBD in vertebrate MRs is of interest because mutations in the LBD have been correlated with changes in transcriptional activation by Aldo and other steroids (Fagart et al 1998, Geller et al 2000, Bledsoe et al 2005, Fagart et al 2005, Bridgham et al 2006, Funder 2013, Shibata et al 2013, Mani 2016).…”

“…F and B, but not Aldo, are found in ray-finned fish (Jiang et al 1998, Sakamoto et al 2011. Aldo first appears in lungfish (Joss et al 1994, Rossier et al 2015, which also secrete F and B. Lungfish are the closest extant forerunners of tetrapods (Woolston 2013). (Rupprecht et al 1993b, Geller 2000 and an agonist for fish MRs (Sturm et al 2005, Pippal et al 2011, Sugimoto et al 2016.…”

“…The EC50s of Aldo, DOC and B for skate MR are 0.07 nM, 0.03 nM and 0.09 nM, respectively (Carroll et al 2008). 11βHSD2 first appears in Chondrichthyes , Rossier et al 2015, in which 11βHSD2 may regulate access of B to the MR. Although Aldo is not found in ray-finned fish, Aldo is a strong transcriptional activator of fish MR (Greenwood et al 2003, Sturm et al 2005, Stolte et al 2008, Pippal et al 2011, Sugimoto et al 2016.…”

“…Thus, during the evolution of the MR in cartilaginous fishes, ray-finned fishes and terrestrial vertebrates, there have been changes in the EC50 of the MR for 3-ketosteroids (Sturm et al 2005, Carroll et al 2008, Pippal et al 2011, Sugimoto et al 2016, as well as the MR's physiological function (Vize & Smith 2004, Hawkins et al 2012, Martinerie et al 2013, Rossier et al 2015, Jaisser & Farman 2016, Mifsud & Reul 2016, Sakamoto et al 2016. It needs to be noted that transcriptional activation by corticosteroids of fish MRs is studied in mammalian cells, which may provide different responses than in assays using homologous fish cells.…”

“…Hydroxylated corticosterone at C18 followed by oxidation of the C18 hydroxyl forms aldosterone. In a second pathway, progesterone is hydroxylated at C17 and then hydroxylated at C21 to form 11-deoxycortisol, which is hydroxylated at C11 to form cortisol (Baker 2011, Rossier et al 2015. Fagart et al 2005, Edman et al 2015 and GR (Bledsoe et al 2002, He et al 2014 and functional studies of human MR mutants (Fagart et al 1998, Geller et al 2000, Bledsoe et al 2005, Shibata et al 2013, Jimenez-Canino et al 2016, Mani 2016 to investigate the evolution of selectivity for Aldo and other corticosteroids by the MR in terrestrial vertebrates (Baker et al 2013) and ray-finned fish (Prunet et al 2006, Bury & Sturm 2007, Arterbery et al 2011, Sugimoto et al 2016, as well as the basis for binding of some glucocorticoids by human MR and other vertebrate MRs , Mani et al 2016.…”