scholarly journals The Angiotensin II Type 1 Receptor-Associated Protein Attenuates Angiotensin II-Mediated Inhibition of the Renal Outer Medullary Potassium Channel in Collecting Duct Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Juliano Zequini Polidoro ◽  
Nancy Amaral Rebouças ◽  
Adriana Castello Costa Girardi
Keyword(s):  
Angiotensin Ii ◽  
Cell Surface ◽  
Collecting Duct ◽  
Cell Surface Expression ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

Adjustments in renal K+ excretion constitute a central mechanism for K+ homeostasis. The renal outer medullary potassium (ROMK) channel accounts for the major K+ secretory route in collecting ducts during basal conditions. Activation of the angiotensin II (Ang II) type 1 receptor (AT1R) by Ang II is known to inhibit ROMK activity under the setting of K+ dietary restriction, underscoring the role of the AT1R in K+ conservation. The present study aimed to investigate whether an AT1R binding partner, the AT1R-associated protein (ATRAP), impacts Ang II-mediated ROMK regulation in collecting duct cells and, if so, to gain insight into the potential underlying mechanisms. To this end, we overexpressed either ATRAP or β-galactosidase (LacZ; used as a control), in M-1 cells, a model line of cortical collecting duct cells. We then assessed ROMK channel activity by employing a novel fluorescence-based microplate assay. Experiments were performed in the presence of 10−10 M Ang II or vehicle for 40 min. We observed that Ang II-induced a significant inhibition of ROMK in LacZ, but not in ATRAP-overexpressed M-1 cells. Inhibition of ROMK-mediated K+ secretion by Ang II was accompanied by lower ROMK cell surface expression. Conversely, Ang II did not affect the ROMK-cell surface abundance in M-1 cells transfected with ATRAP. Additionally, diminished response to Ang II in M-1 cells overexpressing ATRAP was accompanied by decreased c-Src phosphorylation at the tyrosine 416. Unexpectedly, reduced phospho-c-Src levels were also found in M-1 cells, overexpressing ATRAP treated with vehicle, suggesting that ATRAP can also downregulate this kinase independently of Ang II-AT1R activation. Collectively, our data support that ATRAP attenuates inhibition of ROMK by Ang II in collecting duct cells, presumably by reducing c-Src activation and blocking ROMK internalization. The potential role of ATRAP in K+ homeostasis and/or disorders awaits further investigation.

scholarly journals Intracellular Na+ Controls Cell Surface Expression of Na,K-ATPase via a cAMP-independent PKA Pathway in Mammalian Kidney Collecting Duct Cells

2003 ◽  
Vol 14 (7) ◽  
pp. 2677-2688 ◽  
Author(s):  
Manlio Vinciguerra ◽  
Georges Deschênes ◽  
Udo Hasler ◽  
David Mordasini ◽  
Martine Rousselot ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Surface ◽  
Atpase Activity ◽  
Collecting Duct ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cortical Collecting Duct ◽  
Mammalian Kidney ◽  
Duct Cells ◽  
Collecting Duct Cells

In the mammalian kidney the fine control of Na+ reabsorption takes place in collecting duct principal cells where basolateral Na,K-ATPase provides the driving force for vectorial Na+ transport. In the cortical collecting duct (CCD), a rise in intracellular Na+ concentration ([Na+]i) was shown to increase Na,K-ATPase activity and the number of ouabain binding sites, but the mechanism responsible for this event has not yet been elucidated. A rise in [Na+]i caused by incubation with the Na+ ionophore nystatin, increased Na,K-ATPase activity and cell surface expression to the same extent in isolated rat CCD. In cultured mouse mpkCCDcl4 collecting duct cells, increasing [Na+]i either by cell membrane permeabilization with amphotericin B or nystatin, or by incubating cells in a K+-free medium, also increased Na,K-ATPase cell surface expression. The [Na+]i-dependent increase in Na,K-ATPase cell-surface expression was prevented by PKA inhibitors H89 and PKI. Moreover, the effects of [Na+]i and cAMP were not additive. However, [Na+]i-dependent activation of PKA was not associated with an increase in cellular cAMP but was prevented by inhibiting the proteasome. These findings suggest that Na,K-ATPase may be recruited to the cell membrane following an increase in [Na+]i through cAMP-independent PKA activation that is itself dependent on proteasomal activity.

Role of AQP2 during apoptosis in cortical collecting duct cells

2009 ◽  
Vol 101 (4) ◽  
pp. 237-250 ◽  
Author(s):  
Pilar Flamenco ◽  
Luciano Galizia ◽  
Valeria Rivarola ◽  
Juan Fernandez ◽  
Paula Ford ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

Adaptation to alkalosis induces cell cycle delay and apoptosis in cortical collecting duct cells: Role of aquaporin-2

2010 ◽  
Vol 224 (2) ◽  
pp. 405-413 ◽  
Author(s):  
Valeria Rivarola ◽  
Pilar Flamenco ◽  
Luciana Melamud ◽  
Luciano Galizia ◽  
Paula Ford ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Cell Cycle Delay ◽  
Aquaporin 2 ◽  
Duct Cells ◽  
Collecting Duct Cells

Regulation of luminal alkalinization and acidification in the cortical collecting duct by angiotensin II

1995 ◽  
Vol 269 (5) ◽  
pp. F730-F738 ◽  
Author(s):  
I. D. Weiner ◽  
A. R. New ◽  
A. E. Milton ◽  
C. C. Tisher
Keyword(s):  
Angiotensin Ii ◽  
B Cell ◽  
Collecting Duct ◽  
At1 Receptor ◽  
Rate Of Change ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Stop Flow

Angiotensin II (ANG II) regulates whole kidney ion transport, yet its effects in the collecting duct are unknown. The purpose of these studies was to determine whether ANG II regulates luminal alkalinization and acidification in the rabbit cortical collecting duct (CCD). The rate of luminal alkalinization or acidification was measured as the rate of change of luminal fluid pH under stop-flow conditions using in vitro microperfused CCD segments. Outer CCD alkalinized the luminal fluid, consistent with net HCO3- secretion. Addition of ANG II, 10(-7) M, to the peritubular solution for 30 min significantly stimulated luminal alkalinization. The stimulatory effect of ANG II was not due to time-dependent effects and was blocked by peritubular addition of the ANG II type 1 (AT1) receptor antagonist, losartan, at 10(-6) M. Losartan, 10(-6) M, when added to the peritubular solution, did not alter the rate of luminal alkalinization independent of ANG II. In contrast, peritubular ANG II, 10(-7) M, did not alter inner CCD luminal acidification. Addition of ANG II to the peritubular solution at the lower concentration of 10(-10) M did not alter the rates of luminal alkalinization and acidification in the outer and inner CCD, respectively. Peritubular ANG II, 10(-7) M, but not vehicle, stimulated B cell apical HCO3- secretion occurring in response to peritubular Cl- removal. These studies demonstrate that ANG II acts through a basolateral AT1 receptor to stimulate outer CCD luminal alkalinization via, at least in part, B cell stimulation.

Hormone-regulated transepithelial Na+ transport in mammalian CCD cells requires SGK1 expression

2003 ◽  
Vol 284 (3) ◽  
pp. F480-F487 ◽  
Author(s):  
My N. Helms ◽  
Géza Fejes-Tóth ◽  
Anikó Náray-Fejes-Tóth
Keyword(s):  
Mammalian Cells ◽  
Collecting Duct ◽  
Full Length ◽  
Cortical Collecting Duct ◽  
Dexamethasone Treatment ◽  
Duct Cells ◽  
High Insulin ◽  
Collecting Duct Cells ◽  
Phox Homology

To study the role of serum and glucocorticoid-inducible kinase-1 (SGK1) in mammalian cells, we compared Na+ transport rates in wild-type (WT) M1 cortical collecting duct cells with M1 populations stably expressing human full-length SGK1, NH2-terminal truncated (ΔN-60) SGK1, “kinase-dead” (K127M) SGK1, and cells that have downregulated levels of SGK1 mRNA (antisense SGK1). Basal rates of transepithelial Na+ transport were highest in full-length SGK1 populations, compared among the above populations. Dexamethasone treatment increased Na+ transport in WT and full-length SGK1 cells 2.7- and 2-fold, respectively. Modest stimulation of Na+ absorption was detected after dexamethasone treatment in ΔN-60 SGK1 populations. However, ΔN-60 SGK1 transport rates remained substantially lower than WT values. Importantly, a combination of high insulin, dexamethasone, and serum failed to significantly stimulate Na+ transport in antisense or K127M SGK1 cells. Additionally, expression of antisense SGK1 significantly decreased transepithelial resistance values. Overall, we concluded that SGK1 is a critical component in corticosteroid-regulated Na+ transport in mammalian cortical collecting duct cells. Furthermore, our data suggest that the NH2 terminus of SGK1 may contain a Phox homology-like domain that may be necessary for effective Na+transport.

Volume regulation in cortical collecting duct cells: role of AQP2

2005 ◽  
Vol 97 (9) ◽  
pp. 687-697 ◽  
Author(s):  
Paula Ford ◽  
Valeria Rivarola ◽  
Osvaldo Chara ◽  
Marcel Blot-Chabaud ◽  
Françoise Cluzeaud ◽  
...  
Keyword(s):  
Volume Regulation ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells

Abstract 408: Hyperglycemia Increases the Prorenin Receptor in the Plasma Membrane of Collecting Duct Cells in Rats with Type 1 Diabetes Mellitus

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Minolfa C Prieto ◽  
Danielle Y Arita ◽  
Camille T Bourgeois ◽  
Ryousuke Satou
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Ang Ii ◽  
Duct Cells ◽  
Prorenin Receptor ◽  
Collecting Duct Cells ◽  
Tubulointerstitial Inflammation

In type 1 diabetes mellitus (T1DM) there is increased prorenin secretion by the principal cells of the collecting duct. Binding of prorenin to prorenin receptor (PRR) on intercalated cells increases its catalytic activity, increases local angiotensin (Ang) II formation, and stimulates intracellular MAPK signaling responsible for inflammation and tissue fibrosis. Thus, changes in the amount of membrane bound PRR may be a key factor in stimulating these pathways. However, it has not been established that activation of PRR in the collecting duct contributes to increased intrarenal Ang II and tubulointerstitial inflammation via stimulation of inflammatory pathways including transforming growth factor-beta (TGF-β). This study tested the hypothesis that hyperglycemia increases the PRR abundance at the plasma membrane (PM) in the collecting duct cells, thus allowing greater capability to be activated by locally produced prorenin. Streptozotocin (STZ; 60 mg/kg; ip single dose) was used to induce T1DM in Sprague-Dawley rats (N=10) and compared to control rats (N=8). After 7-days induction, STZ-rats showed plasma glucose levels of 428±13 vs. 138±9 mg/dL and insulin of 0.05±0.02 vs. 2.4±0.6 ng/mL, compared to control. Although PRR transcript in the renal medulla were not different between groups; PRR localized predominantly on the apical aspects of collecting duct cells in STZ-induced rats; while in controls it was primarily found intracellularlly. These changes were accompanied by greater levels of active renin and Ang II in the urine and increased TGF-β mRNA levels in the renal medulla of STZ-rats (Renin: 186± 34 vs. 6± 3 ng Ang I/mL/h; P<0.01; Ang II: 884± 147 vs. 42± 14 fmol/h; P<0.05; TGF-β: 1.22 ± 0.06 vs. 0.97 ± 0.03 mRNA ratio; P<0.01). To further assess if hyperglycemia induced in vitro PRR trafficking alterations, collecting duct M-1 cells were treated with normal glucose (NG; 1mM glucose + 1 mM mannitol) and high glucose (HG; 4mM) for 5, 60, and 360 min. PRR protein levels were higher in the PM fractions in cells treated with HG, compared to cells treated with NG. Thus, hyperglycemia increases PRR abundance in the PM of the collecting duct and stimulates TGF-β synthesis in the renal medulla which may underlie the development of tubulointerstitial inflammation.

scholarly journals Angiotensin II increases fibronectin and collagen I through the β-catenin-dependent signaling in mouse collecting duct cells

2015 ◽  
Vol 308 (4) ◽  
pp. F358-F365 ◽  
Author(s):  
Catherina A. Cuevas ◽  
Alexis A. Gonzalez ◽  
Nibaldo C. Inestrosa ◽  
Carlos P. Vio ◽  
Minolfa C. Prieto
Keyword(s):  
Angiotensin Ii ◽  
Target Genes ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Collagen I ◽  
Ang Ii ◽  
Protein Levels ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Gsk 3Β

The contribution of angiotensin II (ANG II) to renal and tubular fibrosis has been widely reported. Recent studies have shown that collecting duct cells can undergo mesenchymal transition suggesting that collecting duct cells are involved in interstitial fibrosis. The Wnt/β-catenin signaling pathway plays an essential role in development, organogenesis, and tissue homeostasis; however, the dysregulation of this pathway has been linked to fibrosis. In this study, we investigated whether AT1receptor activation induces the expression of fibronectin and collagen I via the β-catenin pathway in mouse collecting duct cell line M-1. ANG II (10−7M) treatment in M-1 cells increased mRNA, protein levels of fibronectin and collagen I, the β-catenin target genes (cyclin D1 and c-myc), and the myofibroblast phenotype. These effects were prevented by candesartan, an AT1receptor blocker. Inhibition of the β-catenin degradation with pyrvinium pamoate (pyr; 10−9M) prevented the ANG II-induced expression of fibronectin, collagen I, and β-catenin target genes. ANG II treatment promoted the accumulation of β-catenin protein in a time-dependent manner. Because phosphorylation of glycogen synthase kinase-3β (GSK-3β) inhibits β-catenin degradation, we further evaluated the effects of ANG II and ANG II plus pyr on p-ser9-GSK-3β levels. ANG II-dependent upregulation of β-catenin protein levels was correlated with GSK-3β phosphorylation. These effects were prevented by pyr. Our data indicate that in M-1 collecting duct cells, the β-catenin pathway mediates the stimulation of fibronectin and collagen I in response to AT1receptor activation.

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