Deoxycorticosterone-stimulated bicarbonate secretion in rabbit cortical collecting ducts: effects of luminal chloride removal and in vivo acid loading

1985 ◽  
Vol 249 (2) ◽  
pp. F205-F212 ◽  
Author(s):  
J. Garcia-Austt ◽  
D. W. Good ◽  
M. B. Burg ◽  
M. A. Knepper
Keyword(s):  
Collecting Duct ◽  
High Rate ◽  
Bicarbonate Secretion ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Urinary Ph ◽  
Collecting Ducts ◽  
Acid Loading

To assess the role of cortical collecting duct bicarbonate secretion in the regulation of net acid excretion, we have sought to identify what factors influence the secretion rate. Net and unidirectional bicarbonate fluxes were measured in isolated perfused cortical collecting ducts from deoxycorticosterone-treated rabbits. The collecting ducts secreted bicarbonate at 11-24 pmol X mm-1 X min-1, confirming the high rate seen in earlier studies. Oral acid loading (50 mM NH4Cl drinking water) completely inhibited the net bicarbonate secretion. The bath-to-lumen flux was markedly reduced with acid loading, but the lumen-to-bath flux changed very little. In tubules from rabbits treated with deoxycorticosterone (but not NH4Cl), luminal chloride replacement with either sulfate or gluconate completely and reversibly inhibited the net bicarbonate secretion. The bath-to-lumen flux was greatly inhibited, but there was little change in the lumen-to-bath flux. We conclude: 1) High rates of bicarbonate secretion can be induced in rabbit cortical collecting ducts by chronic treatment of the animals with deoxycorticosterone. 2) When deoxycorticosterone-treated rabbits were made acidotic by oral administration of NH4Cl, the bicarbonate secretion was prevented, indicating that the systemic acid-base state of the animal may be an important factor regulating bicarbonate secretion. 3) Replacement of chloride in the lumen with sulfate inhibits bicarbonate secretion in the cortical collecting duct, an effect which may explain in part the decrease in urinary pH in response to sulfate infusions in mineralocorticoid-stimulated animals.

Evidence of corticosteroid action along the nephron

1984 ◽  
Vol 246 (2) ◽  
pp. F111-F123 ◽  
Author(s):  
D. Marver
Keyword(s):  
Collecting Duct ◽  
Type I ◽  
Type Ii ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Type Iii ◽  
Collecting Ducts ◽  
Collecting Tubule ◽  
Cortical Collecting Tubule

The kidney contains three classes of corticosteroid-binding proteins receptors. They include a mineralocorticoid-specific (Type I), a glucocorticoid-specific (Type II), and a corticosterone-specific (Type III) site. The Type I and Type III sites roughly parallel each other along the nephron, with maximal binding occurring in the late distal convoluted or connecting segment and the cortical and medullary collecting ducts. Type II sites occur throughout the nephron, with maximal concentrations appearing in the proximal tubule and the late distal convoluted-cortical collecting duct region. The function of the Type I sites in the connecting segment is unclear since chronic mineralocorticoid therapy does not influence the potential difference in this segment as it does in the cortical collecting tubule. Furthermore, the specific role of Type II versus Type III sites in the distal nephron is unknown. Finally, the possible influence of sodium on both latent and steroid-induced renal cortical and medullary Na-K-ATPase is discussed.

Cellular actions of cAMP on HCO3(-)-secreting cells of rabbit CCD: dependence on in vivo acid-base status

1994 ◽  
Vol 266 (4) ◽  
pp. F528-F535 ◽  
Author(s):  
C. Emmons ◽  
J. B. Stokes
Keyword(s):  
Anion Exchanger ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Disulfonic Acid ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Acid Base Status

HCO3- secretion by cortical collecting duct (CCD) occurs via beta-intercalated cells. In vitro CCD HCO3- secretion is modulated by both the in vivo acid-base status of the animal and by adenosine 3',5'-cyclic monophosphate (cAMP). To investigate the mechanism of cAMP-induced HCO3- secretion, we measured intracellular pH (pHi) of individual beta-intercalated cells of CCDs dissected from alkali-loaded rabbits perfused in vitro. beta-Intercalated cells were identified by demonstrating the presence of an apical anion exchanger (cell alkalinization in response to removal of lumen Cl-). After 180 min of perfusion to permit decrease of endogenous cAMP, acute addition of 0.1 mM 8-bromo-cAMP or 1 microM isoproterenol to the bath caused a transient cellular alkalinization (> 0.20 pH units). In the symmetrical absence of either Na+, HCO3-, or Cl-, cAMP produced no change in pHi. Basolateral dihydrogen 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) for 15 min before cAMP addition also prevented this alkalinization. In contrast to the response of cells from alkali-loaded rabbits, addition of basolateral cAMP to CCDs dissected from normal rabbits resulted in an acidification of beta-intercalated cells (approximately 0.20 pH units). The present studies demonstrate the importance of the in vivo acid-base status of the animal in the regulation of CCD HCO3- secretion by beta-intercalated cells. The results identify the possible existence of a previously unrecognized Na(+)-dependent Cl-/HCO3- exchanger on the basolateral membrane of beta-intercalated cells in alkali-loaded rabbits.

H(+)-K(+)-ATPase activity in rat collecting duct segments

1992 ◽  
Vol 262 (4) ◽  
pp. F692-F695 ◽  
Author(s):  
J. D. Gifford ◽  
L. Rome ◽  
J. H. Galla
Keyword(s):  
Atpase Activity ◽  
Marked Decrease ◽  
Collecting Duct ◽  
Intercalated Cells ◽  
Cortical Collecting Duct ◽  
Acid Base ◽  
Medullary Collecting Duct ◽  
Gastric Proton Pump

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.

scholarly journals TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct

2007 ◽  
Vol 292 (2) ◽  
pp. F667-F673 ◽  
Author(s):  
Junichi Taniguchi ◽  
Shuichi Tsuruoka ◽  
Atsuko Mizuno ◽  
Jun-ichi Sato ◽  
Akio Fujimura ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cortical Collecting Duct ◽  
Urine Production ◽  
K Secretion ◽  
Distal Tubules ◽  
Transient Receptor

The transient receptor vanilloid-4 (TRPV4) is a mechanosensitive, swell-activated cation channel that is abundant in the renal distal tubules. Immunolocalization studies, however, present conflicting data as to whether TRPV4 is expressed along the apical and/or basolateral membranes. To disclose the role of TRPV4 in flow-dependent K+ secretion in distal tubules in vivo, urinary K+ excretion and net transports of K+ and Na+ in the cortical collecting duct (CCD) were measured with an in vitro microperfusion technique in TRPV4 +/+ and TRPV4 −/− mice. Both net K+ secretion and Na+ reabsorption were flow dependently increased in the CCDs isolated from TRPV4 +/+mice, which were significantly enhanced by a luminal application of 50 μM 4α-phorbol-12,13-didecanoate (4αPDD), an agonist of TRPV4. No flow dependence of net K+ and Na+ transports or effects of 4αPDD on CCDs were observed in TRPV4 −/− mice. A basolateral application of 4αPDD had little effect on these ion transports in the TRPV4 +/+ CCDs, while the luminal application did. Urinary K+ excretion was significantly smaller in TRPV4 −/− than in TRPV4 +/+ mice when urine production was stimulated by a venous application of furosemide. These observations suggested an essential role of the TRPV4 channels in the luminal or basolateral membrane as flow sensors in the mechanism underlying the flow-dependent K+ secretion in mouse CCDs.

Permeabilities of rat collecting duct segments to NH3 and NH4+

1991 ◽  
Vol 260 (2) ◽  
pp. F264-F272 ◽  
Author(s):  
M. F. Flessner ◽  
S. M. Wall ◽  
M. A. Knepper
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Cortical Collecting Duct ◽  
Concentration Gradients ◽  
Apparent Permeability ◽  
Collecting Ducts ◽  
Total Ammonia ◽  
Medullary Collecting Duct ◽  
Set Up

We have measured NH3 and NH4+ permeability coefficients in collecting ducts from the cortex, outer medulla, and inner medulla of the rat kidney. Isolated collecting duct segments of the rat were perfused with bicarbonate-buffered solutions containing carbonic anhydrase to eliminate any pH disequilibrium in the tubule lumen. NH3 or NH4+ concentration gradients were set up between the bath and the lumen. By measuring the total CO2 and total ammonia concentrations in the bath, the perfusate, and collected fluid, the NH3 and NH4+ concentrations were determined. Then, using the flow rate in the tubule and the tubule dimensions, we calculated the apparent permeability in each collecting duct segment for NH3 and NH4+. The NH3 permeabilities were as follows: 0.002 cm/s in the inner medullary collecting duct, 0.012 cm/s in the outer medullary collecting duct, and 0.024 cm/s in the cortical collecting duct. The NH4+ permeabilities for all segments were on the order of 10(-5) cm/s or less. The relative permeability values for the two ammonium species are consistent with the view that the secretion observed in vivo in collecting ducts is due to passive diffusion of NH3 from the interstitium to the lumen of the duct, parallel with H+ secretion.

Role of cell volume variations in Na(+)-K(+)-ATPase recruitment and/or activation in cortical collecting duct

1994 ◽  
Vol 266 (5) ◽  
pp. C1342-C1349 ◽  
Author(s):  
N. Coutry ◽  
N. Farman ◽  
J. P. Bonvalet ◽  
M. Blot-Chabaud
Keyword(s):  
Image Analysis ◽  
Cell Volume ◽  
Specific Activity ◽  
Collecting Duct ◽  
Cell Swelling ◽  
Cortical Collecting Duct ◽  
Pump Unit ◽  
Ouabain Binding ◽  
Collecting Ducts

The aim of this study was to examine whether cell volume variations could play a role in the previously reported Na(+)-K(+)-ATPase pump recruitment and/or activation induced by an increase in intracellular Na concentration (Nai) in cortical collecting ducts (CCD). Isolated CCD from kidneys of aldosterone-repleted mice were incubated in hyper-, hypo-, or isosmotic solutions with and without Na to modify Nai and cell volume independently. Nai, cell volume, and the number of basolateral pumps were measured using 22Na, image analysis, and specific [3H]ouabain binding, respectively. Ouabain-sensitive 86Rb uptake was also measured. In CCD with high Nai, pump recruitment and/or activation was observed only when an increase in tubular volume was associated with Na load. Pump recruitment and/or activation was also induced by cell swelling in the absence of Na load. Recruited and/or activated pumps display an affinity for ouabain and a specific activity (ouabain-sensitive Rb uptake per pump unit) similar to basal pumps. We conclude that 1) cell swelling is implied in the process of Nai-dependent pump recruitment and/or activation, 2) cell swelling can promote pump recruitment and/or activation independently of Na load, 3) basal and recruited and/or activated pumps probably correspond to the same Na(+)-K(+)-ATPase isoform.

Total CO2 transport in rat cortical collecting duct in chloride-depletion alkalosis

1990 ◽  
Vol 258 (4) ◽  
pp. F848-F853 ◽  
Author(s):  
J. D. Gifford ◽  
K. Sharkins ◽  
J. Work ◽  
R. G. Luke ◽  
J. H. Galla
Keyword(s):  
Peritoneal Dialysis ◽  
Metabolic Alkalosis ◽  
Collecting Duct ◽  
Bicarbonate Transport ◽  
Cortical Collecting Duct ◽  
Co2 Transport ◽  
Chloride Depletion

Previous studies in chloride-depletion metabolic alkalosis (CDA) generated by intraperitoneal dialysis have suggested major alterations in chloride and bicarbonate transport beyond the distal convoluted tubule. To investigate the possible role of the cortical collecting duct (CCD) in the pathophysiology of CDA, isolated CCD segments were perfused in vitro from either control (CON) rats dialyzed against Ringer-bicarbonate or those made alkalotic by peritoneal dialysis with 0.15 M NaHCO3. Tubules from CDA animals secreted CO2 for greater than or equal to 3 h after dissection (-22.4 +/- 7.2 pmol.mm-1.min-1) compared with CON tubules that absorbed CO2 (18.3 +/- 4.2 pmol.mm-1.min-1). Replacement of luminal chloride with gluconate in the perfusate abolished net total CO2 (tCO2) secretion in tubules from CDA animals (from -21.5 +/- 4.5 to -2.7 +/- 2.3 pmol.mm-1.min-1) but did not alter net tCO2 absorption in tubules from CON animals. In contrast, removal of bath chloride increased net tCO2 secretion (-12.1 +/- 2.9 to -26.1 +/- 3.6 pmol.mm-1.min-1) in CDA tubules, whereas net tCO2 flux was altered from absorption to secretion in CON tubules (15.5 +/- 4.0 to -13.6 +/- 9.2 pmol.mm-1.min-1). These results demonstrate that 1) CDA generated in vivo within 45 min results in stable net tCO2 secretion in vitro up to 240 min in the CCD; 2) luminal chloride is necessary for tCO2 secretion; 3) the shift of net tCO2 flux from absorption to secretion in CON tubules in vitro was not sustained in contrast to CDA tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Bicarbonate transport by isolated perfused rat collecting ducts

1985 ◽  
Vol 249 (4) ◽  
pp. F485-F489 ◽  
Author(s):  
J. L. Atkins ◽  
M. B. Burg
Keyword(s):  
Regulatory Mechanism ◽  
Collecting Duct ◽  
Bicarbonate Transport ◽  
Bicarbonate Secretion ◽  
Cortical Collecting Duct ◽  
Acid Excretion ◽  
Alkaline Urine ◽  
Acid Urine ◽  
Collecting Ducts

Previously, bicarbonate transport was measured in isolated perfused rabbit cortical collecting ducts (CCD) and outer medullary collecting ducts (OMCD). Rabbit CCD either absorbed or secreted bicarbonate in vitro, depending on whether the animals were treated with NH4Cl or NaHCO3, but the OMCD absorbed bicarbonate regardless of the treatment. The general significance of these findings (particularly the bicarbonate secretion) was questioned because rabbits are herbivores that normally excrete alkaline urine. Therefore, we have now studied rats, an omnivorous species, that normally excrete acid urine. The overall pattern of bicarbonate transport in rats was similar to that previously found in rabbits. CCD from rats given NaHCO3 initially secreted bicarbonate, but those from rats given NH4Cl absorbed bicarbonate. Rat OMCD all absorbed bicarbonate, regardless of the treatment. The significant differences between the results with rats and rabbits were 1) a marked shift in bicarbonate transport in control and bicarbonate-loaded rat (but not rabbit) CCD with time of perfusion in vitro from secretion toward absorption; this implies an additional regulatory mechanism in rats; and 2) rat OMCDs absorbing bicarbonate more than three times faster than rabbit OMCD. These results provide additional evidence that conditioned changes in cortical collecting duct bicarbonate transport, now observed in two different species, play a significant role in the control of net acid excretion.

scholarly journals Increased Na+/H+exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease

2012 ◽  
Vol 302 (10) ◽  
pp. C1436-C1451 ◽  
Author(s):  
Dragos Olteanu ◽  
Xiaofen Liu ◽  
Wen Liu ◽  
Venus C. Roper ◽  
Neeraj Sharma ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Collecting Duct ◽  
Principal Cell ◽  
Cortical Collecting Duct ◽  
Wild Type ◽  
Polycystic Kidney ◽  
Acid Base ◽  
Collecting Ducts ◽  
Mutant Cells

Pathophysiological anomalies in autosomal dominant and recessive forms of polycystic kidney disease (PKD) may derive from impaired function/formation of the apical central monocilium of ductal epithelia such as that seen in the Oak Ridge polycystic kidney or orpk ( Ift88Tg737Rpw) mouse and its immortalized cell models for the renal collecting duct. According to a previous study, Na/H exchanger (NHE) activity may contribute to hyperabsorptive Na+movement in cilium-deficient (“mutant”) cortical collecting duct principal cell monolayers derived from the orpk mice compared with cilium-competent (“rescued”) monolayers. To examine NHE activity, we measured intracellular pH (pHi) by fluorescence imaging with the pH-sensitive dye BCECF, and used a custom-designed perfusion chamber to control the apical and basolateral solutions independently. Both mutant and rescued monolayers exhibited basolateral Na+-dependent acid-base transporter activity in the nominal absence of CO2/HCO3−. However, only the mutant cells displayed appreciable apical Na+-induced pHirecoveries from NH4+prepulse-induced acid loads. Similar results were obtained with isolated, perfused collecting ducts from orpk vs. wild-type mice. The pHidependence of basolateral cariporide/HOE-694-sensitive NHE activity under our experimental conditions was similar in both mutant and rescued cells, and 3.5- to 4.5-fold greater than apical HOE-sensitive NHE activity in the mutant cells (pHi6.23–6.68). Increased apical NHE activity correlated with increased apical NHE1 expression in the mutant cells, and increased apical localization in collecting ducts of kidney sections from orpk vs. control mice. A kidney-specific conditional cilium-knockout mouse produced a more acidic urine compared with wild-type littermates and became alkalotic by 28 days of age. This study provides the first description of altered NHE activity, and an associated acid-base anomaly in any form of PKD.

scholarly journals Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney

2013 ◽  
Vol 305 (7) ◽  
pp. R735-R747 ◽  
Author(s):  
Jacob Richards ◽  
Sean All ◽  
George Skopis ◽  
Kit-Yan Cheng ◽  
Brandy Compton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Target Genes ◽  
Collecting Duct ◽  
Sodium Reabsorption ◽  
Cortical Collecting Duct ◽  
Liver And Kidney ◽  
Dependent Mechanism

Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1–3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes αENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPARα and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney.

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