Possible role of cytosolic calcium and Na-Ca exchange in regulation of transepithelial sodium transport

1979 ◽  
Vol 236 (6) ◽  
pp. F505-F512 ◽  
Author(s):  
A. Taylor ◽  
E. E. Windhager
Keyword(s):  
Sodium Transport ◽  
Calcium Ion ◽  
Critical Role ◽  
Cytosolic Calcium ◽  
Feedback Mechanism ◽  
Toad Urinary Bladder ◽  
Renal Tubules ◽  
Apical Surface ◽  
Negative Feedback Mechanism ◽  
Transepithelial Sodium Transport

Emerging evidence in a number of different epithelia suggests that changes in cytosolic calcium ion levels play a critical role in the regulation of transepithelial sodium transport. Maneuvers believed to raise cytosolic calcium ion activity lead to an inhibition of net sodium transport in toad urinary bladder, frog skin, and isolated perfused proximal renal tubules. Regulation of the level of ionized calcium in the cytosol of the epithelial cells appears to involve a process of coupled Na-Ca exchange across the basolateral plasma membrane, energized, at least in part, by the sodium gradient. It is suggested that changes in cytosolic calcium ion levels, secondary to changes in Na-Ca exchange, in turn dependent in part on the activity of the sodium pump, constitute a link in a negative feedback mechanism. Through such a feedback mechanism, the rate of entry of sodium into the cell across the apical surface may be kept in step with its rate of extrusion across the basolateral surface.

Cytosolic calcium and the action of vasopressin in toad urinary bladder

1987 ◽  
Vol 252 (6) ◽  
pp. F1028-F1041
Author(s):  
A. Taylor ◽  
E. Eich ◽  
M. Pearl ◽  
A. S. Brem ◽  
E. Q. Peeper
Keyword(s):  
Urinary Bladder ◽  
Water Flow ◽  
Sodium Transport ◽  
Short Circuit ◽  
Exchange Process ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Toad Urinary Bladder ◽  
Low Sodium ◽  
Transepithelial Sodium Transport

The effects of experimental procedures believed to increase cytosolic calcium on basal and vasopressin-stimulated osmotic water flow and transepithelial sodium transport were examined in the toad urinary bladder. Exposure of isolated toad bladders to quinidine, calcium ionophores (A23187, X537A), or low-sodium or potassium-free serosal solutions resulted in a dose-dependent decrease in the hydrosmotic response to vasopressin or exogenous adenosine 3',5'-cyclic monophosphate (cAMP). The degree of inhibition of cAMP-induced water flow induced by low-sodium or potassium-free serosal bathing media varied, and in a similar manner, with the serosal calcium concentration. The effects of quinidine sulfate (2 X 10-4 M), X537A (2 X 10(-5) M), and low serosal sodium (20 mM), but not that of A23187 (10(-5) M), were readily reversible. Exposure to quinidine (4 X 10(-4) M), A23187 (10(-5) M), X537A (5 X 10(-6) M), or low serosal sodium (2 mM) also inhibited the basal short-circuit current (SCC). Vasopressin, 4-20 mU/ml, completely overcame the inhibition of the SCC induced by quinidine, A23187, or low serosal sodium, but a submaximal dose of hormone (4 mU/ml) failed to fully reverse the inhibitory effect of X537A, 5 X 10(-6) M. These results are consistent with the view that 1) a Na-Ca exchange process operates across the basolateral surface of the granular epithelial cells of the toad urinary bladder in vivo, and 2) the level of free calcium in the granular cell cytosol plays a modulatory role in the control of apical membrane water and sodium permeability by vasopressin, and in the regulation of the basal rate of transepithelial sodium transport.

Effect of carbenoxolone on glucocorticoid metabolism and Na transport in toad bladder

1989 ◽  
Vol 257 (4) ◽  
pp. F700-F704
Author(s):  
A. S. Brem ◽  
K. L. Matheson ◽  
T. Conca ◽  
D. J. Morris
Keyword(s):  
Sodium Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Water Soluble ◽  
Toad Bladder ◽  
Toad Urinary Bladder ◽  
Base Line ◽  
Target Tissue ◽  
Glucocorticoid Metabolism ◽  
Transepithelial Sodium Transport

In humans, diminished 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme activity has been associated with sodium retention and hypertension. These studies show that the toad bladder, another target tissue epithelium displaying steroid-induced sodium transport, possesses the enzyme 11 beta-OHSD. The toad urinary bladder rapidly transformed corticosterone (3 x 10(-8) M) (50% by 10 min and 90% by 180 min) with 11-dehydrocorticosterone being the major metabolite. The 11-dehydrocorticosterone produced reached an apparent plateau when the tissue incubations were repeated with higher concentrations of corticosterone (10(-7) and 10(-6) M). Carbenoxolone sodium (2.5 x 10(-5) M), a water soluble derivative of glycyrrhetinic acid, markedly inhibited the metabolism of corticosterone (3 x 10(-8) M) to 11-dehydrocorticosterone similar to previous observations in the mammalian kidney. Carbenoxolone sodium (2.5 x 10(-5) M) did not significantly affect short-circuit current (SCC) in toad bladders when added to either the serosal or mucosal bath. However, when carbenoxolone sodium was added to the mucosal bath and 60 min later corticosterone 10(-6) M was placed in the serosal bath, bladders generated a SCC 2.07 +/- 0.17 (mean +/- SE) times above base line at 360 min compared with 1.48 +/- 0.11 in bladders exposed to corticosterone alone (P less than 0.02). In parallel experiments, carbenoxolone sodium in the mucosal bath enhanced the rise in SCC induced by cortisol 10(-6) M; 1.66 +/- 0.16 times above base line at 360 min compared with 1.07 +/- 0.14 with cortisol alone (P less than 0.02). We conclude that the toad bladder contains 11 beta-OHSD and inhibition of this enzyme with carbenoxolone sodium is associated with amplification of glucocorticoid-induced transepithelial sodium transport in this tissue. However, since the quantity of 11-dehydro-product produced appears to be limited, other factors in addition to inhibition of 11 beta-OHSD may play a role in this amplification of sodium transport.

scholarly journals A negative feedback mechanism links UBC gene expression to ubiquitin levels by affecting RNA splicing rather than transcription

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marzia Bianchi ◽  
Rita Crinelli ◽  
Elisa Giacomini ◽  
Elisa Carloni ◽  
Lucia Radici ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Rna Splicing ◽  
Transcription Initiation ◽  
Critical Role ◽  
Feedback Mechanism ◽  
Dependent Manner ◽  
Rna Molecules ◽  
Negative Feedback Mechanism ◽  
Dose Dependent

AbstractUBC gene plays a critical role in maintaining ubiquitin (Ub) homeostasis. It is upregulated under stress conditions, and herein we report that it is downregulated upon Ub overexpression. Downregulation occurs in a dose-dependent manner, suggesting the existence of a fine-tuned Ub sensing mechanism. This “sensor” requires a conjugation competent ubiquitin to detect Ub levels. Searching the sensor among the transcription factors involved in basal and stress-induced UBC gene expression was unsuccessful. Neither HSF1 and HSF2, nor Sp1 and YY1 are affected by the increased Ub levels. Moreover, mutagenesis of their binding sites in the UBC promoter-driven reporter constructs does not impair the downmodulation effect. Epigenetic studies show that H2A and H2B ubiquitination within the UBC promoter region is unchanged upon ubiquitin overexpression. Noteworthy, quantification of nascent RNA molecules excludes that the downmodulation arises in the transcription initiation step, rather pointing towards a post-transcriptional mechanism. Indeed, a significantly higher fraction of unspliced UBC mRNA is detected in ubiquitin overexpressing cells, compared to empty vector transfected cells. Our findings suggest how increasing cellular ubiquitin levels may control the expression of UBC gene by negatively affecting the splicing of its pre-mRNA, providing a straightforward feedback strategy for the homeostatic control of ubiquitin pools.

scholarly journals Atypical Expression of Type 2 Iodothyronine Deiodinase in Thyrotrophs Explains the Thyroxine-Mediated Pituitary Thyrotropin Feedback Mechanism

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1735-1743 ◽  
Author(s):  
Marcelo A. Christoffolete ◽  
Rogério Ribeiro ◽  
Praful Singru ◽  
Csaba Fekete ◽  
Wagner S. da Silva ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Critical Role ◽  
Feedback Mechanism ◽  
Free T4 ◽  
Critical Signal ◽  
Apparent Paradox ◽  
Iodothyronine Deiodinase ◽  
Negative Feedback Mechanism ◽  
Thyroid Secretion

T4, the main product of thyroid secretion, is a critical signal in plasma that mediates the TSH-negative feedback mechanism. As a prohormone, T4 must be converted to T3 to acquire biological activity; thus, type 2 iodothyronine deiodinase (D2) is expected to play a critical role in this feedback mechanism. However, the mechanistic details of this pathway are still missing because, counterintuitively, D2 activity is rapidly lost in the presence of T4 by a ubiquitin-proteasomal mechanism. In the present study, we demonstrate that D2 and TSH are coexpressed in rat pituitary thyrotrophs and that hypothyroidism increases D2 expression in these cells. Studies using two murine-derived thyrotroph cells, TtT-97 and TαT1, demonstrate high expression of D2 in thyrotrophs and confirm its sensitivity to negative regulation by T4-induced proteasomal degradation of this enzyme. Despite this, expression of the Dio2 gene in TαT1 cells is higher than their T4-induced D2 ubiquitinating capacity. As a result, D2 activity and net T3 production in these cells are sustained, even at free T4 concentrations that are severalfold above the physiological range. In this system, free T4 concentrations and net D2-mediated T3 production correlated negatively with TSHβ gene expression. These results resolve the apparent paradox between the homeostatic regulation of D2 and its role in mediating the critical mechanism by which T4 triggers the TSH-negative feedback.

scholarly journals Action of ouabain on sodium transport in toad urinary bladder, Evidence for two pathways for sodium entry.

1975 ◽  
Vol 65 (4) ◽  
pp. 503-514 ◽  
Author(s):  
A L Finn
Keyword(s):  
Urinary Bladder ◽  
Sodium Transport ◽  
Cardiac Glycoside ◽  
Rate Coefficient ◽  
Potential Gradient ◽  
Electrochemical Potential ◽  
Toad Urinary Bladder ◽  
Transepithelial Sodium Transport

The cardiac glycoside ouabain inhibits transepithelial sodium transport in the toad urinary bladder. It is shown that this drug reduces the rate coefficient for sodium exit at the serosal pump site. In addition, ouabain inhibits entry across the mucosal border whenever the electrochemical potential gradient for sodium is made less favorable. The data are interpreted as indicating the existence of two separate pathways for sodium entry, one of which is ouabain inhibitable.

Quantitative single-cell fluorescence imaging of indicator dyes

1993 ◽  
Vol 51 ◽  
pp. 606-607
Author(s):  
David J. Gross ◽  
M礨 G. Mahoney ◽  
Linda L. Slakey
Keyword(s):  
Calcium Ion ◽  
Imaging System ◽  
Critical Role ◽  
Cytosolic Calcium ◽  
Spectral Shift ◽  
Molecular Probes ◽  
Ion Concentration ◽  
Specific Cell ◽  
Fura 2 ◽  
Vascular Smcs

The use of fluorescent molecular probes in combination with quantitative optical microscopy has burgeoned in the past few years due to dramatic advances in both fluorophore design and imaging instrumentation. A number of probes that exhibit fluorescence spectral shifts with ligand binding have been synthesized. Among them is fura-2, which has a high binding affinity for calcium ion and which shows an excitation spectral shift between the calcium-bound and calcium-unbound states. This talk will focus on fura-2-loaded arterial smooth muscle cells (SMC) stimulated to produce temporally and spatially dynamic changes in free cytosolic calcium ion concentration ([Ca2+]i) as measured by a charge-coupled device imaging system.Intracellular Ca2+ is known to play a critical role in the regulation of the contractile state of vascular SMCs. A variety of extracellular agonists have been shown to stimulate transient [Ca2+]i elevation in vascular SMCs; among them are nucleotides that activate specific cell surface receptors.

scholarly journals Estrogen-Negative Feedback and Estrous Cyclicity Are Critically Dependent Upon Estrogen Receptor-α Expression in the Arcuate Nucleus of Adult Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2986-2995 ◽  
Author(s):  
Shel-Hwa Yeo ◽  
Allan E. Herbison
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Arcuate Nucleus ◽  
Critical Role ◽  
Estrogen Receptor Α ◽  
Feedback Mechanism ◽  
Neuron Activity ◽  
Female Mice ◽  
Negative Feedback Mechanism ◽  
Estrous Cyclicity

The location and characteristics of cells within the brain that suppress GnRH neuron activity to contribute to the estrogen-negative feedback mechanism are poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP recombination in estrogen receptor-α (ERα) floxed mice (ERαflox/flox), we aimed to examine the role of ERα-expressing neurons located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism. Bilateral injection of AAV-Cre into the ARN of ERαflox/flox mice (n = 14) resulted in the time-dependent ablation of up to 99% of ERα-immunoreactive cell numbers throughout the rostrocaudal length of the ARN. These mice were all acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous. Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight was not altered in ERαflox/flox mice. After ovariectomy, a significant increment in LH secretion was observed in all genotypes, although its magnitude was reduced in ERαflox/flox mice. Acute and chronic estrogen-negative feedback were assessed by administering 17β-estradiol to mice as a bolus (LH measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later). This demonstrated that chronic estrogen feedback was absent in ERαflox/flox mice, whereas the acute feedback was normal. These results reveal a critical role for ERα-expressing cells within the ARN in both estrous cyclicity and the chronic estrogen negative feedback mechanism in female mice. This suggests that ARN cells provide a key indirect, transsynpatic route through which estradiol suppresses the activity of GnRH neurons.

Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3744-3750 ◽  
Author(s):  
Katriina J. Peltola ◽  
Kirsi Paukku ◽  
Teija L. T. Aho ◽  
Marja Ruuska ◽  
Olli Silvennoinen ◽  
...  
Keyword(s):  
Target Genes ◽  
Critical Role ◽  
Ectopic Expression ◽  
Feedback Mechanism ◽  
Cytokine Signaling ◽  
Inhibitory Effects ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Negative Feedback Mechanism ◽  
Socs Proteins

Abstract Signal transducer and activator of transcription 5 (STAT5) plays a critical role in cytokine-induced survival of hematopoietic cells. One of the STAT5 target genes is pim-1, which encodes an oncogenic serine/threonine kinase. Here we demonstrate that Pim-1 inhibits STAT5-dependent transcription in cells responsive to interleukin-3, prolactin, or erythropoietin. Ectopic expression of Pim-1 in cytokine-dependent FDCP1 myeloid cells results in reduced tyrosine phosphorylation and DNA binding of STAT5, indicating that Pim-1 interferes already with the initial steps of STAT5 activation. However, the Pim-1 kinase does not directly phosphorylate or bind to STAT5. By contrast, Pim-1 interacts with suppressor of cytokine signaling 1 (SOCS1) and SOCS3 and potentiates their inhibitory effects on STAT5, most likely via phosphorylation-mediated stabilization of the SOCS proteins. Thus, both Pim and SOCS family proteins may be components of a negative feedback mechanism that allows STAT5 to attenuate its own activity.

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