Endothelin-1 production by rat inner medullary collecting duct: effect of nitric oxide, cGMP, and immune cytokines

1994 ◽  
Vol 266 (2) ◽  
pp. F291-F297 ◽  
Author(s):  
D. E. Kohan ◽  
E. Padilla
Keyword(s):  
Nitric Oxide ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Mrna Levels ◽  
Endothelin 1 ◽  
Inner Medullary Collecting Duct ◽  
Short And Long Term ◽  
Medullary Collecting Duct ◽  
Necrosis Factor

Nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and endothelin-1 (ET-1) inhibit collecting duct sodium reabsorption. Because the inner medullary collecting duct (IMCD) synthesizes NO and ET-1, we examined NO and cGMP regulation of IMCD ET-1 production. S-nitroso-N-acetylpenicillamine (SNAP, 6 h) increased NO and cGMP and modestly reduced ET-1 release in cultured rat IMCD. Atrial natriuretic peptide or dibutyryl cGMP (6 h exposure to each) also mildly decreased IMCD ET-1 release. In long-term exposure studies, IMCD cells were incubated with tumor necrosis factor (TNF) and interferon-gamma (IFN) up to 72 h. IFN/TNF increased NO and cGMP production while reducing ET-1 release by 84%; N-monomethyl-L-arginine inhibited this effect only marginally, suggesting NO was not primarily involved. IFN alone greatly reduced IMCD ET-1 release and ET-1 mRNA levels. These data indicate that short- and long-term increases in NO and cGMP modestly reduce IMCD ET-1 production. Additionally, IFN potently inhibits IMCD ET-1 release by an undetermined mechanism.

Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct of the Brattleboro rat

2004 ◽  
Vol 286 (2) ◽  
pp. F216-F224 ◽  
Author(s):  
Bas W. M. van Balkom ◽  
Jason D. Hoffert ◽  
Chung-Lin Chou ◽  
Mark A. Knepper
Keyword(s):  
Nitric Oxide ◽  
Adenylyl Cyclase ◽  
Proteomic Analysis ◽  
Collecting Duct ◽  
Immunoblot Analysis ◽  
Long Term Effects ◽  
Inner Medullary Collecting Duct ◽  
Proteomic Approach ◽  
Medullary Collecting Duct

Vasopressin regulates water and solute transport in the renal collecting duct. In addition to short-term regulation of aquaporin-2 trafficking, vasopressin also has long-term effects to regulate the abundances of aquaporins-2 and -3 and β- and γ-subunits of the epithelial sodium channel in collecting duct principal cells. To investigate further the direct and indirect long-term regulatory actions of vasopressin in the inner medullary collecting duct (IMCD), we used a proteomic approach [difference gel electrophoresis (DIGE) coupled with MALDI-TOF identification of differentially expressed protein spots]. DDAVP or vehicle was infused subcutaneously in Brattleboro rats for 3 days, and IMCD cells were purified from the inner medullas for proteomic analysis. Forty-three proteins were found to be regulated in response to vasopressin infusion, including 18 that were increased in abundance, 22 that were decreased, and 3 that were shifted in the gel, presumably because of posttranslational modification. Immunocytochemistry confirmed collecting duct expression of several of the proteins that were identified. Immunoblot analysis of nine of the proteins confirmed the changes seen by the DIGE method. Of these nine proteins, six were increased in response to DDAVP infusion: nitric oxide synthase-2 (NOS2), GRP78, heat shock protein-70, annexin II, glutaminase, and cathepsin D. The remaining three were decreased in response to DDAVP: aldehyde reductase I, adenylyl cyclase VI, and carbonic anhydrase II. The findings point to a role for vasopressin in the coordinate regulation of several determinants of nitric oxide levels (NOS2, arginase II, NADPH oxidase) and of proteins potentially involved in vasopressin escape (adenylyl cyclase VI and G protein-coupled receptor kinase 4).

Functional upregulation of H+-ATPase by lethal acid stress in cultured inner medullary collecting duct cells

1997 ◽  
Vol 273 (4) ◽  
pp. C1194-C1205 ◽  
Author(s):  
Hassane Amlal ◽  
Zhaohui Wang ◽  
Manoocher Soleimani
Keyword(s):  
Collecting Duct ◽  
Acid Stress ◽  
Northern Hybridization ◽  
Mrna Levels ◽  
Inner Medullary Collecting Duct ◽  
Duct Cells ◽  
Acid Load ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
Mutant Cells

The response of H+-ATPase to lethal acid stress is unknown. A mutant strain (called NHE2d) was derived from cultured inner medullary collecting duct cells (mIMCD-3 cells) following three cycles of lethal acid stress. Cells were grown to confluence on coverslips, loaded with 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein, and monitored for intracellular pH (pHi) recovery from an acid load. The rate of Na+-independent pHi recovery from an acid load in mutant cells was approximately fourfold higher than in parent cells ( P < 0.001). The Na+-independent H+ extrusion was ATP dependent and K+ independent and was completely inhibited in the presence of diethylstilbestrol, N, N′-dicyclohexylcarbodiimide, or N-ethylmaleimide. These results indicate that the Na+-independent H+ extrusion in cultured medullary cells is mediated via H+-ATPase and is upregulated in lethal acidosis. Northern hybridization experiments demonstrated that mRNA levels for the 16- and 31-kDa subunits of H+-ATPase remained unchanged in mutant cells compared with parent cells. We propose that lethal acid stress results in increased H+-ATPase activity in inner medullary collecting duct cells. Upregulation of H+-ATPase could play a protective role against cell death in severe intracellular acidosis.

scholarly journals High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression

2016 ◽  
Vol 311 (2) ◽  
pp. R263-R271 ◽  
Author(s):  
Kelly Anne Hyndman ◽  
Courtney Dugas ◽  
Alexandra M. Arguello ◽  
Traci T. Goodchild ◽  
Kathleen M. Buckley ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Collecting Duct ◽  
High Salt ◽  
Receptor Expression ◽  
Electrolyte Balance ◽  
No Production ◽  
Inner Medullary Collecting Duct ◽  
Nitrite Production ◽  
Vasa Recta ◽  
Medullary Collecting Duct

The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct-derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption.

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct

1991 ◽  
Vol 69 (6) ◽  
pp. 771-775 ◽  
Author(s):  
U. Honrath ◽  
D. R. Wilson ◽  
H. Sonnenberg
Keyword(s):  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Significant Difference ◽  
Collecting Tubule ◽  
Before And After ◽  
K Secretion ◽  
Medullary Collecting Duct ◽  
K Concentration ◽  
Cortical Collecting Tubule

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via β-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the β-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 μg/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.Key words: rat, KCl infusion, potassium transport, fluid reabsorption, sodium reabsorption, chloride reabsorption, catecholamines.

Ligand-dependent regulation of NPR-A gene expression in inner medullary collecting duct cells

1998 ◽  
Vol 275 (1) ◽  
pp. F119-F125 ◽  
Author(s):  
Li Cao ◽  
Song Cang Chen ◽  
Tong Cheng ◽  
Michael H. Humphreys ◽  
David G. Gardner
Keyword(s):  
Gene Expression ◽  
Natriuretic Peptide ◽  
Cell Population ◽  
Promoter Activity ◽  
Collecting Duct ◽  
Receptor Activity ◽  
Regulatory Control ◽  
Mrna Levels ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct

Atrial natriuretic peptide (ANP) interacts with high-affinity, guanylyl cyclase-linked receptors in the inner medullary collecting duct (IMCD), where it exerts important regulatory control over sodium handling. We sought to determine whether receptor activity in these cells would be modulated (downregulated) by prolonged exposure to ligand. A number of natriuretic peptides (ANP, brain natriuretic peptide, and urodilatin) were found to decrease ligand-dependent natriuretic peptide receptor A (NPR-A) activity in IMCD cells. This inhibition was in direct proportion to their capacity to increase basal cGMP levels in this cell population. The reduction in receptor activity was accompanied by a dose- and time-dependent reduction in NPR-A mRNA levels in these cells. The decrease in transcript levels arose, in part, from a reduction in NPR-A gene transcription. ANP reduced NPR-A gene promoter activity in a transiently transfected IMCD cell population. 8-Bromo-cGMP was also effective in inhibiting NPR-A mRNA levels and NPR-A promoter activity, suggesting that the second messenger (i.e., cGMP) rather than ANP, itself, is responsible for downregulation of NPR-A gene expression.

scholarly journals Distinct regulation of inner medullary collecting duct nitric oxide production from mice and rats

2013 ◽  
Vol 40 (3) ◽  
pp. 233-239 ◽  
Author(s):  
Kelly A Hyndman ◽  
Jing Xue ◽  
Alexander MacDonell ◽  
Joshua S Speed ◽  
Chunhua Jin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Collecting Duct ◽  
Nitric Oxide Production ◽  
Inner Medullary Collecting Duct ◽  
Oxide Production ◽  
Medullary Collecting Duct

Atrial natriuretic peptide and nitric oxide signaling antagonizes vasopressin-mediated water permeability in inner medullary collecting duct cells

2009 ◽  
Vol 297 (3) ◽  
pp. F693-F703 ◽  
Author(s):  
Jens Klokkers ◽  
Patrik Langehanenberg ◽  
Björn Kemper ◽  
Sebastian Kosmeier ◽  
Gert von Bally ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Plasma Membrane ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Water Permeability ◽  
Collecting Duct ◽  
Cell Swelling ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct ◽  
Atrial Natriuretic

AVP and atrial natriuretic peptide (ANP) have opposite effects in the kidney. AVP induces antidiuresis by insertion of aquaporin-2 (AQP2) water channels into the plasma membrane of collecting duct principal cells. ANP acts as a diuretic factor. An ANP- and nitric oxide (NO)/soluble guanylate cyclase (sGC)-induced insertion of AQP2 into the plasma membrane is reported from different models. However, functional data on the insertion of AQP2 is missing. We used primary cultured inner medullary collecting duct (IMCD) cells and digital holographic microscopy, calcein-quenching measurements, and immunofluorescence and Western blotting to analyze the effects of ANP and NO donors on AQP2 phosphorylation, membrane expression, and water permeability. While AVP led to acceleration in osmotically induced swelling, ANP had no effect. However, in AVP-pretreated cells ANP significantly decreased the kinetics of cell swelling. This effect was mimicked by 8-bromo-cGMP and blunted by PKG inhibition. Stimulation of the NO/sGC pathway or direct activation of sGC with BAY 58-2667 had similar effects to ANP. In cells treated with AVP, AQP2 was predominantly localized in the plasma membrane, and after additional incubation with ANP AQP2 was mostly localized in the cytosol, indicating an increased retrieval of AQP2 from the plasma membrane by ANP. Western blot analysis showed that ANP was able to reduce AVP-induced phosphorylation of AQP2 at position S256. In conclusion, we show that the diuretic action of ANP or NO in the IMCD involves a decreased localization of AQP2 in the plasma membrane which is mediated by cGMP and PKG.

scholarly journals Flow stimulates inner medullary collecting duct endothelin‐1 production

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Meghana Pandit ◽  
Gabriele L Gusella ◽  
Rajeev Rohatgi ◽  
Donald E Kohan
Keyword(s):  
Collecting Duct ◽  
Endothelin 1 ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct
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