Peritubular AVP regulates bicarbonate reabsorption in cortical distal tubule via V1 and V2receptors

2002 ◽  
Vol 282 (2) ◽  
pp. F256-F264 ◽  
Author(s):  
Raif Musa-Aziz ◽  
Maria Luisa Morais Barreto-Chaves ◽  
Margarida De Mello-Aires
Keyword(s):  
Receptor Antagonist ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Ion Exchange Resin ◽  
Capillary Perfusion ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Dose Dependent

10.1152/ajprenal.00056.2001. Peritubular arginine vasopressin (AVP) regulates bicarbonate reabsorption in the cortical distal tubule via V1 and V2 receptors. The dose-dependent effects of peritubular AVP on net bicarbonate reabsorption ( J HCO[Formula: see text] ) were evaluated by stationary microperfusion of in vivo early (ED; distal convoluted tubule) and late distal (LD; connecting tubule and initial collecting duct) segments of rat kidney, using double-barreled H+-sensitive, ion-exchange resin/reference (1 M KCl) microelectrodes. AVP (10−11 M) perfused into peritubular capillaries increased J HCO[Formula: see text] , compared with basal levels during intact capillary perfusion with blood, in ED and LD segments. AVP (10−9 M) also increased J HCO[Formula: see text] in both segments, but the effect of AVP (10−11 M) was significantly higher. A specificV1-receptor antagonist alone or with AVP (10−11 or 10−9 M) reduced J HCO[Formula: see text] below basal levels. A specific V2-receptor antagonist alone or plus AVP (10−11 M) did not affect J HCO[Formula: see text] but increased AVP (10−9 M)-mediated stimulation. 8-Bromoadenosine 3′,5′-cyclic monophosphate alone reduced J HCO[Formula: see text] below basal levels and also reduced AVP (10−11 M)-mediated stimulation. (Deamino-Cys1, d-Arg8) vasopressin (a V2-selective agonist) also reduced J HCO[Formula: see text] below basal levels. These results show that peritubular AVP stimulates J HCO[Formula: see text] in ED and LD segments via basolateral V1 receptors and that basolateral V2 receptors have a dose-dependent inhibitory effect mediated by cAMP. The data also indicate that endogenous AVP stimulates distal J HCO[Formula: see text] via basolateral V1 receptors.

Direct action of aldosterone on bicarbonate reabsorption in in vivo cortical proximal tubule

2009 ◽  
Vol 296 (5) ◽  
pp. F1185-F1193 ◽  
Author(s):  
Patricia Silva Pergher ◽  
Deise Leite-Dellova ◽  
Margarida de Mello-Aires
Keyword(s):  
Proximal Tubule ◽  
Direct Action ◽  
Rat Kidney ◽  
Free Calcium ◽  
Mineralocorticoid Receptor Antagonist ◽  
Control Value ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Inhibitor Of Protein Synthesis

The direct action of aldosterone (10−12 M) on net bicarbonate reabsorption ( JHCO3−) was evaluated by stationary microperfusion of an in vivo middle proximal tubule (S2) of rat kidney, using H ion-sensitive microelectrodes. Aldosterone in luminally perfused tubules caused a significant increase in JHCO3− from a mean control value of 2.84 ± 0.08 [49/19 ( n° of measurements/ n° of tubules)] to 4.20 ± 0.15 nmol·cm−2·s−1 (58/10). Aldosterone perfused into peritubular capillaries also increased JHCO3−, compared with basal levels during intact capillary perfusion with blood. In addition, in isolated perfused tubules aldosterone causes a transient increase of cytosolic free calcium ([Ca2+]i), monitored fluorometrically. In the presence of ethanol (in similar concentration used to prepare the hormonal solution), spironolactone (10−6 M, a mineralocorticoid receptor antagonist), actinomycin D (10−6 M, an inhibitor of gene transcription), or cycloheximide (40 mM, an inhibitor of protein synthesis), the JHCO3− and the [Ca2+]i were not different from the control value; these drugs also did not prevent the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. However, in the presence of RU 486 alone [10−6 M, a classic glucocorticoid receptor (GR) antagonist], a significant decrease on JHCO3− and on [Ca2+]i was observed; this antagonist also inhibited the stimulatory effect of aldosterone on JHCO3− and on [Ca2+]i. These studies indicate that luminal or peritubular aldosterone (10−12 M) has a direct nongenomic stimulatory effect on JHCO3− and on [Ca2+]i in proximal tubule and that probably GR participates in this process. The data also indicate that endogenous aldosterone stimulates JHCO3− in middle proximal tubule.

Oxytocin affects apical sodium conductance in rabbit cortical collecting duct

1993 ◽  
Vol 265 (4) ◽  
pp. F487-F503 ◽  
Author(s):  
T. Inoue ◽  
M. Naruse ◽  
M. Nakayama ◽  
K. Kurokawa ◽  
T. Sato
Keyword(s):  
Receptor Antagonist ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Physiological Role ◽  
Free Calcium ◽  
Second Phase ◽  
Dependent Manner ◽  
Cortical Collecting Duct ◽  
Acetoxymethyl Ester ◽  
Dose Dependent

The physiological role of oxytocin (OT) in the kidney is still unclear, although autoradiographic data have shown the existence of OT receptors in the rat kidney. We examined the effect of OT in the microperfused rabbit cortical collecting duct (CCD) by using conventional cable analysis and microscope photometry. On addition of 10(-9) M OT to the bath, the lumen-negative transepithelial voltage (VT) transiently increased and the transepithelial resistance (RT) and the fractional resistance of the apical membrane (FRA) (1st phase) both decreased. After this initial change, the lumen-negative VT gradually decreased below its baseline level and RT and FRA (second phase) both increased. These electrical changes were dose dependent and were prevented by the addition of 10(-5) M amiloride to the lumen. Although responses to OT were not prevented by 10(-9) M arginine vasopressin (AVP) or 10(-6) M of a V1-receptor antagonist (OPC-21268) or V2-receptor antagonist (OPC-31260), they were inhibited by the addition of the specific OT antagonist des-Gly-NH2-[d(CH2)3,Tyr(Me),Thr]OVT. Additional studies of intracellular free calcium ([Ca2+]i) revealed that 10(-8)-10(-6) M OT caused an increase in [Ca2+]i in CCD in a dose-dependent manner. Also, pretreatment with 2 x 10(-8) M bis-(aminophenoxy)ethane-tetraacetic acid-acetoxymethyl ester, an intracellular Ca2+ chelator, abolished the electrical and [Ca2+]i responses to OT. Pretreatment with 5 x 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) partially prevented the electrical responses to OT, thus reducing the decrease in lumen-negative VT below its basal level and the increase in RT after the 1st phase. These data show that OT affects the apical Na+ conductance of collecting duct cells through OT receptors distinct from the AVP receptors and that the effect of OT may, at least in part, be brought about by a mechanism(s) dependent on the increase in [Ca2+]i and cAMP production.

scholarly journals In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

2010 ◽  
Vol 299 (6) ◽  
pp. F1473-F1485 ◽  
Author(s):  
Daniel Ackermann ◽  
Nikolay Gresko ◽  
Monique Carrel ◽  
Dominique Loffing-Cueni ◽  
Daniel Habermehl ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Glucocorticoid Receptors ◽  
Nuclear Translocation ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Plasma Aldosterone ◽  
Thick Ascending Limb ◽  
Cell Nuclei

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.

Determination of disequilibrium pH in the rat kidney in vivo: evidence of hydrogen secretion

1981 ◽  
Vol 240 (2) ◽  
pp. F138-F146 ◽  
Author(s):  
T. D. DuBose ◽  
L. R. Pucacco ◽  
N. W. Carter
Keyword(s):  
Carbonic Anhydrase ◽  
Metabolic Alkalosis ◽  
Rat Kidney ◽  
Respiratory Acidosis ◽  
Distal Tubule ◽  
Distal Nephron ◽  
Bicarbonate Reabsorption ◽  
Disequilibrium Ph ◽  
Tubule Fluid

The recent demonstration of elevated PCO2 in structures of the rat renal cortex indicated that previous determinations of disequilibrium pH (pHDq), and thus the differentiation of H+ secretion from bicarbonate reabsorption per se, required further evaluation. A new aspiration pH electrode was developed to allow tubule fluid to achieve chemical equilibrium at the PCO2 prevailing in vivo. In control and bicarbonate-loaded rats a pHDq was not observed in either proximal or distal tubules. After intravenous benzolamide a significant acid pHDq was observed in the proximal (but not the distal) nephron, and increased further during metabolic alkalosis. During combined metabolic alkalosis and respiratory acidosis a significant pHDq was present in the distal but not in the proximal tubule. Aldosterone administration to bicarbonate-loaded, hypercapnic rats did not alter the distal pHDq further. When present, the pHDq in the distal tubule was obliterated by carbonic anhydrase infusion. We conclude that proximal but not distal tubule fluid is in functional contact with carbonic anhydrase; the enzyme is in excess in the proximal lumen and H2CO3 did not accumulate even during conditions associated with increased H+ secretion; the basal rate of H+ secretion in the distal nephron accessible to cortical micropuncture is less than previously assumed. The data support the view that H+ secretion is the major mechanism of renal bicarbonate reabsorption.

Application of the disequilibrium pH method to investigate the mechanism of urinary acidification

1983 ◽  
Vol 245 (5) ◽  
pp. F535-F544
Author(s):  
T. D. DuBose
Keyword(s):  
Metabolic Alkalosis ◽  
Collecting Duct ◽  
Respiratory Acidosis ◽  
Distal Tubule ◽  
Bicarbonate Reabsorption ◽  
Urinary Acidification ◽  
Technological Advances ◽  
Papillary Collecting Duct ◽  
Disequilibrium Ph

DuBose, Thomas D., Jr. Application of the disequilibrium pH method to investigate the mechanism of urinary acidification. Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F535-F544, 1983.--The cellular mechanism of renal bicarbonate reabsorption has been debated for four decades. Recent technological advances have allowed distinction between primary bicarbonate reabsorption and a proton secretory mechanism. The disequilibrium pH method has been applied widely for this purpose and has supported the latter hypothesis uniformly. The demonstration of elevated values for PCO2 in tubular and vascular structures of the renal cortex has not altered this view. Indeed, by employing a newly developed method for measurement of equilibrium pH in vivo that permits contact with the environment within the tubule lumen to continue, we demonstrated an acid disequilibrium pH in the proximal tubule after carbonic anhydrase inhibition equal to -0.68 pH units. A spontaneous disequilibrium pH was not present in the distal tubule during control conditions or during metabolic alkalosis but was demonstrated during combined respiratory acidosis-metabolic alkalosis. This finding agrees qualitatively with observed rates of bicarbonate reabsorption in the perfused distal tubule in vivo. With use of similar techniques, an acid disequilibrium pH in conjunction with elevated values for PCO2 was observed in the papillary collecting duct. Thus, proton secretion appears to be the predominant mechanism of bicarbonate reabsorption in superficial nephrons and explains, as well, the means by which the urine-to-blood PCO2 gradient in alkaline urine is established.

Direct effects of endothelin in the rat kidney

1990 ◽  
Vol 258 (2) ◽  
pp. F397-F402 ◽  
Author(s):  
T. Katoh ◽  
H. Chang ◽  
S. Uchida ◽  
T. Okuda ◽  
K. Kurokawa
Keyword(s):  
Renal Artery ◽  
Rat Kidney ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Left Renal Artery ◽  
Dependent Manner ◽  
Direct Effects ◽  
Dose Dependent

In the present study, we tested the direct effects of endothelin (ET) on rat kidney in vivo. ET was infused into the left renal artery of anesthetized rats at a rate of 0.5, 5, 20, or 40 pmol/h. ET reduced ipsilateral urine volume (V), clearance of inulin (CIN), and clearance of p-aminohippuric acid (CPAH) in a dose-dependent manner. Thus ET at 20 pmol/h did not change V but decreased renal plasma flow (RPF) and glomerular filtration rate (GFR) by 27.6 +/- 14.3 and 30.8 +/- 10.4%, respectively, in the ipsilateral kidney. ET at 0.5 pmol/h was without effect and at 5 pmol/h had only minor effects on CIN and CPAH of ipsilateral kidney. At 40 pmol/h, ET reduced ipsilateral V, GFR, and RPF by 52.3 +/- 21.4, 58.4 +/- 14.5, and 72.5 +/- 10.6%, respectively. Filtration fraction and fractional excretion of Na remained unchanged during ET infusion. ET, 40 pmol/h, infused into the renal artery together with atrial natriuretic peptide (ANP) at a rate of 12 pmol/h reduced the ipsilateral V, GFR, and RPF by 33.2 +/- 6.3, 26.1 +/- 6.0, and 27.2 +/- 7.1%, respectively, decrements less than those with ET alone. When a calcium-channel blocker nicardipine was infused at a rate of 2.5 micrograms/h into the renal artery together with ET, 20 pmol/h, there was little change in the ipsilateral V, RPF, and GFR; ET, 40 pmol/h, with nicardipine did not change V and decreased GFR and RPF by 25.9 +/- 5.6 and 23.1 +/- 10.8%, respectively, decrements less than those without nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Urodilatin: binding properties and stimulation of cGMP generation in rat kidney cells

1993 ◽  
Vol 264 (2) ◽  
pp. F267-F273
Author(s):  
H. Saxenhofer ◽  
W. R. Fitzgibbon ◽  
R. V. Paul
Keyword(s):  
Guanylate Cyclase ◽  
Mesangial Cells ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Binding Characteristics ◽  
Papillary Collecting Duct ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
Anp Receptors

Urodilatin (URO) [ANP-(95-126)] is an analogue of atrial natriuretic peptide (alpha-ANP) [ANP-(99-126)] that was first isolated from human urine. In rat mesangial cells, URO competed with high affinity for non-guanylate cyclase-coupled ANPR-C receptors [concentration at which 50% labeled ligand is displaced (IC50) approximately 70 pM], but with lesser affinity to the guanylate cyclase-linked ANPR-A receptors (IC50 approximately 800 pM). alpha-ANP bound to both receptors with similar affinity [dissociation constant (Kd) approximately 150 pM]. In papillary collecting duct homogenates, which possess only ANPR-A receptors, the apparent Kd value averaged 229 pM for alpha-ANP and 2.7 nM for URO. Intravenous URO was at least as potent and effective as alpha-ANP in inducing diuresis and natriuresis in anesthetized rats, but URO was approximately 10-fold less potent in stimulating guanosine 3',5'-cyclic monophosphate generation in mesangial and inner medullary collecting duct cells. We conclude that URO has a lesser affinity than alpha-ANP for guanylate cyclase-coupled ANP receptors in the kidney and that the relative natriuretic potency of URO in vivo cannot be directly attributed to its binding characteristics with ANPR-A receptors.

AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex

2001 ◽  
Vol 281 (5) ◽  
pp. F958-F965 ◽  
Author(s):  
Inho Jo ◽  
Donald T. Ward ◽  
Michelle A. Baum ◽  
John D. Scott ◽  
Vincent M. Coghlan ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Regulatory Subunit ◽  
Relative Molecular Mass ◽  
Signaling Complex ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit

We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes purified from rat kidney IMCD contain the type II protein kinase A (PKA) regulatory subunit (RII), protein phosphatase (PP)2B, PKCζ, and an RII-binding protein (relative molecular mass ∼90 kDa) representing a putative A kinase anchoring protein (AKAP). Affinity chromatography of detergent-solubilized endosomes on cAMP-agarose permits recovery of a protein complex consisting of the 90-kDa AKAP, RII, PP2B, and PKCζ. With the use of small-particle flow cytometry, RII and PKCζ were localized to an identical population of endosomes, suggesting that these proteins are components of an endosomal multiprotein complex.32P-labeled aquaporin-2 (AQP2) present in these PKA-phosphorylated endosomes was dephosphorylated in vitro by either addition of exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar to that described previously in hippocampal neurons. This signaling complex potentially mediates the phosphorylation of AQP2 to regulate its trafficking into the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling complex could also dephosphorylate AQP2 in vivo.

Mechanism of acidification along cortical distal tubule of the rat

1994 ◽  
Vol 266 (2) ◽  
pp. F218-F226 ◽  
Author(s):  
R. Fernandez ◽  
M. J. Lopes ◽  
R. F. de Lira ◽  
W. F. Dantas ◽  
E. J. Cragoe Junior ◽  
...  
Keyword(s):  
Channel Blocker ◽  
Exchange Resin ◽  
Rat Kidney ◽  
Specific Inhibitor ◽  
Distal Tubule ◽  
Ringer Solution ◽  
Na Channel ◽  
Bafilomycin A1 ◽  
Bicarbonate Reabsorption ◽  
Distal Tubules

The cellular mechanism of luminal acidification (bicarbonate reabsorption) was studied in cortical distal tubules of rat kidney. The stopped-flow microperfusion technique was applied to early distal (ED) and late distal (LD) segments, perfused with bicarbonate Ringer solution to which specific inhibitors were added, to measure bicarbonate reabsorption [HCO3 flux (JHCO3)]. pH and transepithelial potential difference (Vt) were recorded by double-barreled H+ exchange resin/reference (1 M KCl) electrodes. Amiloride increased stationary pH and reduced Vt in both early and late segments. Hexamethylene-amiloride (HMA), a specific Na(+)-H+ exchange blocker, reduced JHCO3 in both segments (ED by 43.6 and LD by 40.3%) without affecting Vt. Benzamil, an Na(+)-channel blocker, reduced Vt by 75.9 in ED and 74.9% in LD but had no significant effect on acidification in both segments. The specific inhibitor of H(+)-ATPase, bafilomycin A1, inhibited LD JHCO3 at a concentration of 2 x 10(-7) M by 49%, but ED was inhibited by 24% only at 2 x 10(-6) M. Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase, reduced JHCO3 by 35% in LD of K(+)-depleted rats but not in control rats and had no effect on ED. These data indicate that, in ED, bicarbonate reabsorption is mediated mostly by Na(+)-H+ exchange. In LD, there is evidence for contribution of Na(+)-H+ exchange, vacuolar H(+)-ATPase, and H(+)-K(+)-ATPase (in K(+)-depleted rats) to bicarbonate reabsorption.

scholarly journals Uroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway

2014 ◽  
Vol 307 (6) ◽  
pp. C532-C541 ◽  
Author(s):  
Vanessa da Silva Lima ◽  
Renato O. Crajoinas ◽  
Luciene R. Carraro-Lacroix ◽  
Alana N. Godinho ◽  
João L. G. Dias ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Distal Tubule ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Camp Content ◽  
Bicarbonate Reabsorption ◽  
Guanylate Cyclase C ◽  
Dependent Pathway

Cumulative evidence suggests that guanylin peptides play an important role on electrolyte homeostasis. We have previously reported that uroguanylin (UGN) inhibits bicarbonate reabsorption in a renal distal tubule. In the present study, we tested the hypothesis that the bicarbonaturic effect of UGN is at least in part attributable to inhibition of H+-ATPase-mediated hydrogen secretion in the distal nephron. By in vivo stationary microperfusion experiments, we were able to show that UGN inhibits H+-ATPase activity by a PKG-dependent pathway because KT5823 (PKG inhibitor) abolished the UGN effect on distal bicarbonate reabsorption and H89 (PKA inhibitor) was unable to prevent it. The in vivo results were confirmed by the in vitro experiments, where we used fluorescence microscopy to measure intracellular pH (pHi) recovery after an acid pulse with NH4Cl. By this technique, we observed that UGN and 8 bromoguanosine-cGMP (8Br-cGMP) inhibited H+-ATPase-dependent pHi recovery and that the UGN inhibitory effect was abolished in the presence of the PKG inhibitor. In addition, by using RT-PCR technique, we verified that Madin-Darby canine kidney (MDCK)-C11 cells express guanylate cyclase-C. Besides, UGN stimulated an increase of both cGMP content and PKG activity but was unable to increase the production of cellular cAMP content and PKA activity. Furthermore, we found that UGN reduced cell surface abundance of H+-ATPase B1 subunit in MDCK-C11 and that this effect was abolished by the PKG inhibitor. Taken together, our data suggest that UGN inhibits H+-ATPase activity and surface expression in renal distal cells by a cGMP/PKG-dependent pathway.

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