Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ

2006 ◽  
Vol 291 (4) ◽  
pp. F714-F721 ◽  
Author(s):  
Vivek Bhalla ◽  
Rama Soundararajan ◽  
Alan C. Pao ◽  
Hongyan Li ◽  
David Pearce
Keyword(s):  
Sodium Transport ◽  
Functional Significance ◽  
Early Phase ◽  
Mineralocorticoid Receptor ◽  
Tonic Inhibition ◽  
Sodium Reabsorption ◽  
Transport Regulation ◽  
Tight Epithelia ◽  
New Evidence ◽  
Stimulation Of

Regulation of ENaC occurs at several levels. The principal hormonal regulator of ENaC, aldosterone, acts through the mineralocorticoid receptor to modulate ENaC-mediated sodium transport, and considerable attention has focused on defining the components of the early phase of this response. Two genes, SGK1 and GILZ, have now been implicated in this regulation. While the functional significance of SGK1 in mediating aldosterone effects is well established, new evidence has enhanced our understanding of the mechanisms of SGK1 action. In addition, recent work demonstrates a novel role for GILZ in the stimulation of ENaC-mediated sodium transport. Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia.

Phosphatidylinositol 3,4,5-trisphosphate: an early mediator of insulin-stimulated sodium transport in A6 cells

2004 ◽  
Vol 287 (2) ◽  
pp. F319-F328 ◽  
Author(s):  
Nicolas Markadieu ◽  
Daniel Blero ◽  
Alain Boom ◽  
Christophe Erneux ◽  
Renaud Beauwens
Keyword(s):  
Sodium Transport ◽  
Cell Monolayer ◽  
Sodium Reabsorption ◽  
Na Channel ◽  
Insulin Stimulation ◽  
Cell Monolayers ◽  
A6 Cells ◽  
Cell Extracts ◽  
Pkb Phosphorylation ◽  
Stimulation Of

Insulin stimulates sodium transport across A6 epithelial cell monolayers. Activation of phosphatidylinositol 3-kinase (PI 3-kinase) was suggested as an early step in the insulin-stimulated sodium reabsorption (Ref. 35). To establish that the stimulation of the PI 3-kinase signaling cascade is causing stimulation of apical epithelial Na channel, we added permeant forms of phosphatidylinositol (PI) phosphate (P) derivatives complexed with a histone carrier to A6 epithelium. Only PIP3 and PI( 3 , 4 )P2 but not PI( 4 , 5 )P2 stimulated sodium transport, although each of them penetrated into A6 cell monolayers as assessed using fluorescent permeant phosphoinositides derivatives. By Western blot analysis of A6 cell extracts, the inositol 3-phosphatase PTEN and the protein kinase B PKB were both detected. To further establish that the stimulation of sodium transport induced by insulin is related to PIP3 levels, we transfected A6 cells with human PTEN cDNA and observed a 30% decrease in the natriferic effect of insulin. Similarly, the increase in sodium transport observed by addition of permeant PIP3 was also reduced by 30% in PTEN-overexpressing cells. PKB, a main downstream effector of PI 3-kinase, was phosphorylated at both Thr 308 and Ser 473 residues upon insulin stimulation of the A6 cell monolayer. PKB phosphorylation in response to insulin stimulation was reduced in PTEN-overexpressing cells. Permeant PIP3 also increased PKB phosphorylation. Taken together, the present results establish that the d-3-phosphorylated phosphoinositides PIP3 and PI( 3 , 4 )P2 mediate the effect of insulin on sodium transport across A6 cell monolayers.

Use of Isolated Tight Epithelia to Study the Site and Mode of Drug Action on Cell Membrane Transport: Effect of the Antipsychotic Agent Trifluoperazine

1990 ◽  
Vol 17 (3) ◽  
pp. 224-227
Author(s):  
Henning F. Bjerregaard
Keyword(s):  
Cell Membrane ◽  
Toxic Effect ◽  
Membrane Transport ◽  
Antipsychotic Agent ◽  
Na Transport ◽  
Tight Epithelia ◽  
Acute Toxic Effect ◽  
Cell Membrane Transport ◽  
Dose Dependent ◽  
Stimulation Of

The aim of the present study was to investigate the site and mode of trifluoperazine (TFP) action on cell membrane transport by the use of isolated frog skin. This cellular system gives access to the apical (outer) and basolateral (inner) membranes of the polarised epithelial cells. Both apical and basolateral TFP addition induced a dose-dependent stimulation of Na transport, and depolarised the cellular potential. The data indicate that TFP acts by increasing the Na permeability of the apical membrane. However, the mechanisms localised in the apical and basolateral membranes are quite different. Basolateral TFP addition increased Na transport due to a stimulation of PGE2 synthesis, whereas apical TFP addition abolished Na inhibition of the apical Na channels, and thereby enhanced the Na transport. An acute toxic effect on the electrophysiological parameters was noted after addition of high apical TFP concentrations (50–100μM). This toxic effect was dependent on the presence of Na in the apical solution.

Stimulation of Sodium Transport by Oxidants in Middle Ear Epithelium in Primary Culture

1995 ◽  
Vol 115 (2) ◽  
pp. 291-295 ◽  
Author(s):  
Tzong-Yang Tu ◽  
Claude Amiel ◽  
Patrice Tran Ba Huy ◽  
Philippe Herman
Keyword(s):  
Primary Culture ◽  
Middle Ear ◽  
Sodium Transport ◽  
Stimulation Of

Possible new evidence for Mid-Pleistocene glaciation in the Vale of Pickering, North Yorkshire, UK

2021 ◽  
pp. pygs2020-019
Author(s):  
William A. Fairburn ◽  
Mark D. Bateman
Keyword(s):  
Ice Sheet ◽  
Luminescence Dating ◽  
Marine Isotope Stage ◽  
Pleistocene Glaciation ◽  
Infra Red ◽  
Geomorphic Features ◽  
Ice Field ◽  
Sand And Gravel ◽  
New Evidence ◽  
Stimulation Of

Whilst the Late Devensian glaciation (MIS2) of the Vale of Pickering is well-documented, earlier glaciations within it are not. A proposed limited glaciation in the Mid-Pleistocene, thought to be of Marine Isotope Stage 8 (MIS) age is not well constrained. This paper aimed to obtain preliminary ages for two of the most prominent geomorphic features in the Vale of Pickering to see if they related to pre-Devensian glaciations. New luminescence dating by infra-red stimulation of feldspars from sand accumulations near the summit of Gallows Hill, part of the Wykeham Moraine, and from a section through poorly sorted fluvial sand and gravel on the flanks of the Hutton Buscel Terrace in Yedman Dale gave ages of 176±14 ka and 156±12 ka respectively. Evidence suggests they represent a glacial incursion (MIS 6) into the Vale of Pickering blocking its eastern end and forming a pre-Devensian Glacial Lake Pickering. Whilst they could be older, this style of glaciation is very different to the limited plateau ice-field proposed for MIS 8 at the western end of the Vale of Pickering. Taken at face value, these preliminary ages suggest that the Vale of Pickering was partially glaciated in MIS 6 as part of a wider ice-sheet and contemporary with the Saalian glaciation in Europe.

Refractoriness of toad bladder to stimulation of sodium transport

1972 ◽  
Vol 223 (1) ◽  
pp. 104-109 ◽  
Author(s):  
SA Mendoza ◽  
F Murad ◽  
JS Handler ◽  
J Orloff
Keyword(s):  
Sodium Transport ◽  
Toad Bladder ◽  
Stimulation Of

scholarly journals Mechanistic Insights in NeuroD Potentiation of Mineralocorticoid Receptor Signaling

2019 ◽  
Vol 20 (7) ◽  
pp. 1575 ◽  
Author(s):  
Lisa van Weert ◽  
Jacobus Buurstede ◽  
Hetty Sips ◽  
Isabel Mol ◽  
Tanvi Puri ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mood Disorders ◽  
Chromatin Remodeling ◽  
Mineralocorticoid Receptor ◽  
Protective Factor ◽  
Specific Binding ◽  
Transcription Factor Family ◽  
Direct Stimulation ◽  
The Brain ◽  
Stimulation Of

Mineralocorticoid receptor (MR)-mediated signaling in the brain has been suggested as a protective factor in the development of psychopathology, in particular mood disorders. We recently identified genomic loci at which either MR or the closely related glucocorticoid receptor (GR) binds selectively, and found members of the NeuroD transcription factor family to be specifically associated with MR-bound DNA in the rat hippocampus. We show here using forebrain-specific MR knockout mice that GR binding to MR/GR joint target loci is not affected in any major way in the absence of MR. Neurod2 binding was also independent of MR binding. Moreover, functional comparison with MyoD family members indicates that it is the chromatin remodeling aspect of NeuroD, rather than its direct stimulation of transcription, that is responsible for potentiation of MR-mediated transcription. These findings suggest that NeuroD acts in a permissive way to enhance MR-mediated transcription, and they argue against competition for DNA binding as a mechanism of MR- over GR-specific binding.

Regulation of basolateral K channels in proximal tubule studied during continuous microperfusion

1993 ◽  
Vol 264 (3) ◽  
pp. F496-F501 ◽  
Author(s):  
J. S. Beck ◽  
A. M. Hurst ◽  
J. Y. Lapointe ◽  
R. Laprade
Keyword(s):  
Potassium Channel ◽  
Sodium Transport ◽  
Basolateral Membrane ◽  
Ph Sensitive ◽  
Cell Swelling ◽  
Channel Activity ◽  
Open Probability ◽  
Nephron Segments ◽  
Inwardly Rectifying ◽  
Stimulation Of

Potassium channel activity of the basolateral membrane of the collagenase-treated rabbit proximal convoluted tubule (PCT) was studied during continuous luminal microperfusion. In cell-attached patches (high-K pipette) an inwardly rectifying potassium channel was observed with an inward slope conductance of 60.8 +/- 3.3 pS (n = 12) and outward slope conductance of 17.1 +/- 2.7 pS (n = 6). Stimulation of transcellular sodium transport with luminal glucose and alanine increased channel activity [measured as single-channel open probability (NPo)] from 0.19 +/- 0.11 to 0.44 +/- 0.09 (n = 8). This increase in channel activity was not likely to be mediated by either cell depolarization or cell swelling, because channel activity was voltage insensitive over physiological potentials and because the channel was not activated by stretch. However, channel activity was pH sensitive; reducing luminal pH from 7.4 to 6.5 reduced NPo from 0.63 +/- 0.24 to 0.26 +/- 0.16 (n = 5). Our work demonstrates the feasibility of patch clamping the basolateral membrane of microperfused nephron segments. This has allowed us to follow the activity of this potassium channel during an increase in sodium transport and show that its activity does increase during this maneuver. We conclude that: 1) it is possible to patch clamp the basolateral membrane of microperfused nephron segments, and 2) basolateral membrane of the rabbit PCT contains an inwardly rectifying, pH-sensitive potassium channel. The behavior of this channel on stimulation of transcellular sodium transport could explain the macroscopic increase in basolateral potassium conductance observed under similar conditions.

scholarly journals Mechanisms of EGF-induced stimulation of sodium reabsorption by alveolar epithelial cells

1998 ◽  
Vol 275 (1) ◽  
pp. C82-C92 ◽  
Author(s):  
Spencer I. Danto ◽  
Zea Borok ◽  
Xiao-Ling Zhang ◽  
Melissa Z. Lopez ◽  
Paryus Patel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelium ◽  
Alveolar Epithelial Cells ◽  
Cell Labeling ◽  
Northern Analysis ◽  
Sodium Reabsorption ◽  
Alveolar Epithelial ◽  
Subunit Mrna ◽  
Epidermal Growth ◽  
Stimulation Of

We investigated the effects of epidermal growth factor (EGF) on active Na+ absorption by alveolar epithelium. Rat alveolar epithelial cells (AEC) were isolated and cultivated in serum-free medium on tissue culture-treated polycarbonate filters. mRNA for rat epithelial Na+ channel (rENaC) α-, β-, and γ-subunits and Na+ pump α1- and β1-subunits were detected in day 4 monolayers by Northern analysis and were unchanged in abundance in day 5 monolayers in the absence of EGF. Monolayers cultivated in the presence of EGF (20 ng/ml) for 24 h from day 4 to day 5 showed an increase in both α1 and β1Na+ pump subunit mRNA but no increase in rENaC subunit mRNA. EGF-treated monolayers showed parallel increases in Na+ pump α1- and β1-subunit protein by immunoblot relative to untreated monolayers. Fixed AEC monolayers demonstrated predominantly membrane-associated immunofluorescent labeling with anti-Na+ pump α1- and β1-subunit antibodies, with increased intensity of cell labeling for both subunits seen at 24 h following exposure to EGF. These changes in Na+ pump mRNA and protein preceded a delayed (>12 h) increase in short-current circuit (measure of active transepithelial Na+transport) across monolayers treated with EGF compared with untreated monolayers. We conclude that EGF increases active Na+ resorption across AEC monolayers primarily via direct effects on Na+ pump subunit mRNA expression and protein synthesis, leading to increased numbers of functional Na+ pumps in the basolateral membranes.

Intracellular Redistribution of Sodium and Calcium During Stimulation of Sodium Transport in Epithelial Cells

1968 ◽  
Vol 51 (5) ◽  
pp. 290-302 ◽  
Author(s):  
José A. Zadunaisky ◽  
Joseph F. Gennaro ◽  
Nasser Bashirelahi ◽  
Mary Hilton
Keyword(s):  
Epithelial Cells ◽  
Sodium Transport ◽  
Stimulation Of
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