scholarly journals Mechanisms of WNK1 and WNK4 interaction in the regulation of thiazide-sensitive NaCl cotransport

2005 ◽  
Vol 115 (5) ◽  
pp. 1379-1387 ◽  
Author(s):  
Chao-Ling Yang ◽  
Xiaoman Zhu ◽  
Zhaohong Wang ◽  
Arohan R. Subramanya ◽  
David H. Ellison
Keyword(s):  
Nacl Cotransport

Absence of a cAMP-mediated antiabsorptive effect in an undifferentiated jejunal epithelium

1987 ◽  
Vol 252 (6) ◽  
pp. G776-G782
Author(s):  
R. J. MacLeod ◽  
J. R. Hamilton
Keyword(s):  
Small Intestine ◽  
Thymidine Kinase ◽  
Jejunal Mucosa ◽  
Ussing Chambers ◽  
Luminal Membrane ◽  
Viral Enteritis ◽  
Transmissible Gastroenteritis ◽  
Camp Levels ◽  
Nacl Cotransport

In the relatively undifferentiated jejunal mucosa occurring in piglet viral enteritis, we measured the response of transepithelial Na+ and Cl- fluxes in vitro to raised intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. At the acute 40-h stage of transmissible gastroenteritis (TGE), luminal membrane markers, sucrase and lactase, and a basolateral jejunal epithelial membrane marker Na+-K+-ATPase, were significantly decreased in activity, while a proliferative marker, thymidine kinase, was significantly enriched; these enzyme characteristics are typical of enterocytes isolated from crypts of other species. As expected, control piglet jejunum in short-circuited Ussing chambers after theophylline (10 mM) developed significant net secretory Na and Cl fluxes primarily due to significant antiabsorptive effects (delta JNa m----s = 3.48 +/- 0.52, delta JCl m----s = 2.59 +/- 0.28). Furosemide (10(-4) M), an inhibitor of electroneutral NaCl cotransport, produced antiabsorptive effects (delta JNa m----s = 2.53 +/- 0.31, delta JCl m----s = 2.58 +/- 0.28) in control jejunum that were not significantly different from those seen in response to theophylline. TGE jejunum, however, responded to theophylline not by an antiabsorptive effect but by significant electrogenic Cl- secretion (delta JCl s----m = 1.59 +/- 0.48); furosemide had no effect on ion fluxes in TGE tissue. Control and TGE jejunal mucosal homogenates did not differ in their basal or theophylline-stimulated levels of cAMP. We conclude that the relatively undifferentiated small intestine occurring in acute TGE does not generate either a cAMP-mediated antiabsorptive effect or a furosemide-mediated antiabsorptive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Passive NaCl transport in the flounder urinary bladder: predominance of a cellular pathway

1988 ◽  
Vol 255 (2) ◽  
pp. F229-F236 ◽  
Author(s):  
J. B. Stokes
Keyword(s):  
Urinary Bladder ◽  
High Resistance ◽  
Apical Membrane ◽  
Winter Flounder ◽  
Ionic Diffusion ◽  
Nacl Transport ◽  
Cellular Pathway ◽  
Ionic Conductances ◽  
Transepithelial Voltage ◽  
Nacl Cotransport

The urinary bladder of the winter flounder is a high-resistance epithelium that can absorb Na and Cl in an electrically silent manner. This active absorption (mucosa-to-serosa) of NaCl is, apparently uniquely, inhibited by mucosal hydrochlorothiazide (HCTZ). These experiments evaluated the notion that virtually all of the cellular Na and Cl permeation could be inhibited by mucosal HCTZ. Mucosal Ba2+ reduced the transepithelial conductance from 0.74 +/- 0.08 to 0.60 +/- 0.06 mS/cm2. Mucosal HCTZ reduced the serosa-to-mucosa flux (backflux) of Na from 0.70 +/- 0.08 to 0.29 +/- 0.03 mueq.cm-2.h-1 and the backflux of Cl from 1.92 +/- 0.22 to 0.38 +/- 0.03 mueq.cm-2.h-1. The treatment with these two agents caused the sum of the partial ionic conductances for Na and Cl to approximate the measured transepithelial conductance. In response to the imposition of a transepithelial voltage, the HCTZ-insensitive Na and Cl backfluxes behaved largely as predicted by the laws of simple ionic diffusion, although there was still a detectable cellular backflux. As judged from dilution voltages and tracer fluxes, the diffusional (paracellular) pathway(s) is nonselective for Na and Cl. The HCTZ-sensitive cellular Na and Cl backfluxes are dependent on the presence of mucosal Na and Cl. Neither backflux is significantly inhibited by serosal application of commonly used inhibitors of Na or Cl transport. The results demonstrate that the majority of passive Na and Cl flux is via a cellular pathway. The translocation across the apical membrane probably involves the same NaCl cotransport process responsible for NaCl absorption.

scholarly journals Catecholamine-induced transport systems in trout erythrocyte. Na+/H+ countertransport or NaCl cotransport?

1986 ◽  
Vol 87 (4) ◽  
pp. 551-566 ◽  
Author(s):  
F Borgese ◽  
F Garcia-Romeu ◽  
R Motais
Keyword(s):  
Anion Exchange ◽  
Band 3 ◽  
Cell Swelling ◽  
Transport Systems ◽  
Band 3 Protein ◽  
Free Medium ◽  
Exchange System ◽  
Nucleated Red Blood Cells ◽  
Nacl Cotransport ◽  
Na Uptake

It has previously been shown (Baroin, A., F. Garcia-Romeu, T. Lamarre, and R. Motais. 1984a, b. Journal of Physiology. 350:137, 356:21; Mahé, Y., F. Garcia-Romeu, and R. Motais. 1985. European Journal of Pharmacology. 116:199) that the addition of catecholamines to an isotonic suspension of nucleated red blood cells of the rainbow trout first stimulates a cAMP-dependent, amiloride-sensitive Na+/H+ exchange. This stimulation seems to be transient. It is followed by a more permanent activation of a coupled entry of Na+ and Cl-, which is inhibited by amiloride but also by inhibitors of band 3 protein (DIDS, furosemide, niflumic acid). The coupled entry of Na+ and Cl- could therefore result from the parallel and simultaneous exchange of Na+out for H+in (via the cAMP-dependent Na+/H+ antiporter) and Cl- out for HCO3- in (via the anion exchange system located in band 3 protein). However, in view of the following arguments, it had been proposed that NaCl uptake does not proceed by the double-exchanger system but via an NaCl cotransport: (a) Na+ entry requires Cl- as anion (in NO3- medium, the Na uptake is strongly inhibited, whereas NO3- is an extremely effective substitute for Cl- in the anion exchange system); (b) Na uptake is not significantly affected by the presence of HCO3- in the suspension medium despite the fact that in red cells, Cl-/HCO3- exchange occurs more readily than the exchanges of Cl- for basic equivalents in a theoretically CO2-free medium (the so-called Cl-/OH- exchanges). The purpose of the present paper was a reassessment of the two models by using monensin, an ionophore allowing Na+/H+ exchange. From this study, it appears that NaCl entry results from the simultaneous functioning of the Na+/H+ antiporter and the anion exchange system. The apparent Cl dependence is explained by the fact that, in these erythrocytes, NO3- clearly inhibits the turnover rate of the Na+/H+ antiporter. As Na+/H+ exchange is the driving component in the salt uptake process, this inhibition explains the Cl requirement for Na entry. The lack of stimulation of cell swelling by bicarbonate is explained by the fact that the rate of anion exchange in a CO2-free medium (Cl-/OH- exchange) is roughly equivalent to that of Na+/H+ exchange and thus in practice is not limiting to the net influx of NaCl through the two exchangers.(ABSTRACT TRUNCATED AT 400 WORDS)

Anion-stimulated ATPase in locust rectal epithelium

1988 ◽  
Vol 66 (2) ◽  
pp. 431-438 ◽  
Author(s):  
R. A. Lechleitner ◽  
J. E. Phillips
Keyword(s):  
Alkaline Phosphatase ◽  
Plasma Membrane ◽  
Atpase Activity ◽  
Microsomal Fraction ◽  
Leucine Aminopeptidase ◽  
Mitochondrial Fraction ◽  
Mitochondrial Enzymes ◽  
Differential Centrifugation ◽  
Succinate Cytochrome C Reductase ◽  
Nacl Cotransport

The rectum, the main reabsorptive site in the locust excretory system, actively transports Cl−. This Cl− absorption is electrogenie, not dependent on Na+or [Formula: see text] and insensitive to inhibitors of NaCl cotransport or [Formula: see text] exchange. To determine if active Cl− transport across rectal epithelia might be due to an anion-stimulated ATPase, a microsomal fraction was obtained by differential centrifugation. Microsomal ATPase activity was stimulated in the following sequence: sulphite > bicarbonate > chloride. Maximal ATPase activity was obtained at 25 mM [Formula: see text] or 25 mM Cl−. Thiocyanate (10 mM) inhibited 90% of the anion-stimulated ATPase activity. The microsomal fraction was enriched in the plasma membrane markers, leucine aminopeptidase, alkaline phosphatase, 5′-nucleotidase, and γ-glutamyItranspeptidase, and had little contamination of the mitochondrial enzymes, succinate cytochrome c reductase and cytochrome oxidase. Na,K-ATPase was enriched in the mitochondrial fraction. Microscopic examination confirmed that basolateral membranes were associated with mitochondria following differential centrifugation, while the microsomal fraction contained little mitochondrial contamination. These results indicate the presence of an anion-stimulated ATPase activity that could be responsible for active Cl− transport across locust recta.

Alpha 2-adrenergic, but not imidazole, agonists activate NaCl cotransport in rabbit tracheal epithelial cells

1993 ◽  
Vol 264 (3) ◽  
pp. C568-C576 ◽  
Author(s):  
C. M. Liedtke ◽  
J. Furin ◽  
P. Ernsberger
Keyword(s):  
High Specificity ◽  
Total Density ◽  
Na Transport ◽  
Tracheal Epithelial Cells ◽  
Site Model ◽  
High Affinity ◽  
Tracheal Epithelial ◽  
Dose Dependent Increase ◽  
Camp Levels ◽  
Nacl Cotransport

The adrenergic agonist clonidine activates NaCl cotransport in rabbit tracheocytes. With the use of the high-affinity analogue p-[125I]iodoclonidine, binding of clonidine to cells was determined to fit a two-site model, with one site of high specificity for alpha 2-adrenergic (alpha 2-AR) and the other with a high affinity for I1-imidazol(in)e (I1) receptors. Total density of binding sites for both receptors was similar at 18 fmol/mg protein. Moxonidine displayed a 166-fold greater specificity for I1 receptors compared with cimetidine. Bumetanide-sensitive Na or Cl transport was stimulated by the alpha 2-AR agonists clonidine or guanabenz but not by the I1 agents cimetidine or moxonidine. I1 agonists-stimulated Na transport was detected only in the presence of bumetanide. Prazosin did not block clonidine-stimulated NaCl uptake or efflux, indicating the presence of an alpha 2A-AR subtype. Addition of clonidine either before or after incubation with l-isoproterenol or forskolin did not attenuate the time- and dose-dependent increase in adenosine 3',5'-cyclic monophosphate (cAMP) levels. Thus clonidine stimulates NaCl cotransport in rabbit tracheocytes through an alpha 2A-AR mechanism that does not require cAMP for signal transduction. In addition, I1-imidazol(in)e receptors stimulate Na transport in rabbit tracheocytes through an unidentified pathway.

Acute respiratory acidosis: large-dose furosemide and cerebrospinal fluid ions

1994 ◽  
Vol 76 (6) ◽  
pp. 2651-2655 ◽  
Author(s):  
S. Javaheri ◽  
W. Corbett ◽  
J. M. Adams ◽  
P. J. Davis ◽  
P. S. Gartside
Keyword(s):  
Cerebrospinal Fluid ◽  
Large Dose ◽  
Ionic Composition ◽  
Respiratory Acidosis ◽  
Control Group ◽  
Mechanically Ventilated ◽  
Group I ◽  
Serial Serum ◽  
Group Ii ◽  
Nacl Cotransport

NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.

Sensitivity of cAMP-stimulated salt secretion in shark rectal gland to "loop" diuretics

1984 ◽  
Vol 246 (3) ◽  
pp. C242-C246 ◽  
Author(s):  
H. C. Palfrey ◽  
P. Silva ◽  
F. H. Epstein
Keyword(s):  
Inhibitory Concentration ◽  
Rectal Gland ◽  
Phenoxyacetic Acid ◽  
Shark Rectal Gland ◽  
Avian Erythrocyte ◽  
Cotransport System ◽  
Related Series ◽  
Relative Potencies ◽  
Nacl Cotransport ◽  
Salt Secretion

The secretory response of isolated perfused shark rectal gland was characterized with respect to its inhibition by a chemically related series of 5-sulfamoylbenzoic acid derivatives and certain phenoxyacetic acid derivatives. Maximal fluid and salt secretion was elicited with dibutyryl adenosine 3',5'-cyclic monophosphate and theophylline. The potency series established for the 5-sulfamoylbenzoic acid compounds agreed well with the relative potencies previously established for these agents as inhibitors of Na+-K+-Cl- cotransport in the avian erythrocyte. The most potent compound tested (3-benzylamino-4-phenyl-5-sulfamoylbenzoic acid) had a 50% inhibitory concentration value of approximately 5 X 10(-7) M. This compound was approximately 10-fold more effective than bumetanide and 400-fold as inhibitory as furosemide in this system. Ethacrynic acid (EA; 10(-3) M) was a poor inhibitor of rectal gland secretion and was approximately equipotent with its saturated derivative, dihydro EA. In contrast, EA-L-cysteine was fully effective at 10(-4) M, although the EA-D-cysteine adduct was ineffective. These data also qualitatively agree with results obtained in the inhibition of avian erythrocyte Na+-K+-Cl- cotransport and suggest that the rectal gland possesses a serosally oriented “NaCl cotransport” system with pharmacological and perhaps physiological similarities to the Na+-K+-Cl-cotransporter found in erythrocyte and other cell membranes.

Regulation of apical membrane ion transport in Necturus gallbladder

1992 ◽  
Vol 263 (1) ◽  
pp. C187-C193 ◽  
Author(s):  
J. L. Garvin ◽  
K. R. Spring
Keyword(s):  
Epithelial Cells ◽  
Apical Membrane ◽  
Cell Swelling ◽  
Gallbladder Epithelium ◽  
Necturus Gallbladder ◽  
Camp Levels ◽  
Nacl Cotransport ◽  
Cl Conductance ◽  
Membrane Potential Difference ◽  
Membrane Ion Transport

Na and Cl movement through the apical membrane of Necturus gallbladder epithelium was investigated using electrophysiological and light microscopic measurements. Changes in membrane potential difference, fractional resistance of the apical membrane, and transepithelial resistance caused by changes in apical bath Cl concentration revealed the presence of a Cl conductance in the apical membrane of control tissues that was apparently not present in the preparations studied by other investigators. This Cl conductance was blocked by bumetanide (10(-5) M) or by the inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP) action, the Rp isomer of adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS; 0.5 mM). Treatment of the tissues with Rp-cAMPS also eliminated bumetanide-sensitive cell swelling in the presence of ouabain and activated an amiloride-sensitive swelling, changes consistent with inhibition of NaCl cotransport and the activation of Na-H and Cl-HCO3 exchange. We conclude that the mode of NaCl entry into Necturus gallbladder epithelial cells is determined by the level of cAMP. When cAMP levels are high, entry occurs by NaCl cotransport; when cAMP levels are low, parallel exchange of Na-H and Cl-HCO3 predominates. These observations explain the previous disagreements about the mode of NaCl entry into Necturus gallbladder epithelial cells.

Sign in / Sign up

Export Citation Format

Share Document