Inhibition of the Bicarbonate Exit Step in Urinary Acidification by a Disulfonic Stilbene

Cohen, Loren H.; Mueller, Alan L.; Steinmetz, Philip R.

doi:10.1172/jci109023

Cited by 60 publications

(20 citation statements)

References 21 publications

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“…Similar conclusions have been suggested by a recent study of in vitro, isolated, perfused, rabbit proximal convoluted tubules (57). The turtle bladder also has a conductive pathway for bicarbonate diffusion across the serosal membrane (32,33), and SITS inhibits anion transport on that side of either tissue (32,33,36). We cannot rule out an effect on the pertibular membrane in our studies because large concentrations of the drugs were used, and some fraction may have been reabsorbed and affected peritubular anion transport.…”

Section: Neutral Sodium Chloride Transportsupporting

confidence: 76%

“…The effects of furosemide upon electrogenic sodium reabsorption were examined in the last series of (27) found that 1 mM furosemide reduced volume reabsorption by 50% in the perfused rat ileum. Similar doses of furosemide (1)(2)(3)(4)(5) mM) also inhibit chloride transport across the erythrocyte membrane (28,29), primarily by inhibiting an anion exchange and transport in many physiological systems (30)(31)(32)(33)(34)(35)(36) …”

Section: Methodsmentioning

confidence: 99%

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Effects of Anion-Transport Inhibitors on NaCl Reabsorption in the Rat Superficial Proximal Convoluted Tubule

Lucci¹,

Warnock²

1979

J. Clin. Invest.

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A B S T R A C T The effects of anion-transport inhibitors on volume reabsorption, and total CO2 concentrations were examined by in vivo microperfusion of superficial proximal convoluted tubules of rats. The luminal perfusion solution was a high-chloride, lowbicarbonate solution like that in the in vivo late proximal tubule. The anion-transport inhibitors were only added to the luminal perfusion solutions.In tubules perfused with the control high-chloride solution, the rate of volume reabsorption (J,) was 2.3±0.2 nl/mm min (n = 18), and the collected total CO2 concentration was 4.0±0.3 mM. Furosemide (3 mM) caused a marked reduction in volume reabsorption to 0.8±0.3 nl/mmmin (n = 20) and only a slight increase in the total CO2 concentration of collected samples of perfusate (7.8±0.5 mM). 0.8 mM acetazolamide caused a more pronounced rise in the collected total CO2 concentrations to 10.7±0.5 mM but only a slight fall in J, to 1.7±0.3 nl/mm-min (n = 19). Hence, we inferred that inhibition of carbonic anhydrase only partially accounted for the inhibition of J, by furosemide. 4-acetamido-4'-iso-thiocyanato-stilbene-2,2'-disulphonic acid (0.1 mM), a well-characterized inhibitor of erythrocyte anion exchange mechanisms, also reduced J, to 1.6±0.3 nl/mm min (n = 15) without changing the total CO2 concentrations of the collected perfusates (3.6±0.4 mM). The effect of 4-acetamidoA4'-iso-thiocyanato-stilbene-2,2'-disulphonicPortions of this work were presented at the 10th Annual

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Section: Neutral Sodium Chloride Transportsupporting

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Effects of Anion-Transport Inhibitors on NaCl Reabsorption in the Rat Superficial Proximal Convoluted Tubule

Lucci¹,

Warnock²

1979

J. Clin. Invest.

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“…II]. Obviously, the DMO method simply enables the qual itative indication of the changes in mean cell pH in the tissue but falls short of giving a precise estimation of cytosolic pH in a particular group of cells when a heterogeneous tissue is evaluated: the various cell types that compose the turtle urinary bladder have different pH values as demonstrated by the relatively alkaline cell pH recently shown to be present in the CA-rich cells [10].…”

Section: Role O F Cell Phmentioning

confidence: 99%

“…Gluck et al [16] have shown that a low ambient pH docs not stimulate the H ' ATPase isolated from the fresh-water turtle bladder. Depres sion by carbonic anhydrase (CA) inhibitors of both H ' and HCO3 secretion in tight urinary epithelia results in variable changes in intra cellular acidity, often in the opposite direc tion to those expected if cytosolic pH were a major regulator of JH ' and JHCOj [30], Although the effects of sulfones on JH ' have been attributed to their effect on cell pH [10], the almost complete inhibition of mucosal acidification by a disulfonic stilbene is ac companied by only a minimal change in the [Ht ] in the cytosol. Moreover, the pH gra dient necessary to nullify H+ secretion is the same regardless of the magnitude of JH + and of the CO2 level, indicating that substantial changes in cell pH cannot be invoked as the cause of changes in mucosal acidification in response to CO2 [3], In addition, the notion that intracellular acidosis stimulates JH ' needs to be reconciled with biochemical evi dence that the maximal activity of a number of H+ ATPase of membrane origin is at alkal ine pH [21],…”

Section: Introductionmentioning

confidence: 99%

Marginal Effect of Changes in Acid-Base Status in vitro on Rheogenic H+ and HCO-3 Secretion in Turtle Urinary Bladder

Adrogué¹,

Tasby²,

Ulate³

1987

Kidney Blood Press Res

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This study systematically evaluates the effect of changes in the acid-base composition of the incubation media on the electrogenic H⁺ and HCO^-₃ secretion (voltage clamp method and serosal ouabain) in the isolated turtle urinary bladder. Since the various cell types would change their acidity in a similar direction but to a variable degree, measured mean cell pH values (5, 5-dimethyl-2,3-oxazolidinedione method) were used for an overall assessment of the changes in the acid-base status of the acid-transporting cells. Although addition of exogenous CO₂ (0.7–3%) increased H⁺ secretion (JH⁺) 2- to 4-fold from a CCVfree control period, a further increase in the percent of CO₂ did not enhance JH⁺ demonstrating a permissive but not a stimulatory role of CO₂. Cyclic AMP plus 3-isobutyl-l-methylxanthine-induced electrogenic HCO₃ secretion (JHCO^-₃) remained unaltered at 10% CO₂ from a 5% CO₂ control period. Cell acidosis resulting from either alterations in the PCO₂/HCO^-₃ levels or from NH4CI in the bathing solution did not enhance JH⁺; by contrast maximal levels of acidification were found at cell pH values of about 7.40 and comparable effects on JH+ were found with a variety of PCO₂/HCO^-₃ combinations that led to a similar intracellular acidity.

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“…SITS (4-isothiocyano-4'-acetamido-2,2'-disulfonic stilbene) has been shown to inhibit urinary acidification [2,3]. This inhibition is due to interference with the efflux of bicarbonate across the serosal membrane [2]. We therefore examined the effects of this agent on the exchange flows of chloride and bicarbonate.…”

mentioning

confidence: 99%

Pathways for bicarbonate transfer across the serosal membrane of turtle urinary bladder: Studies with a disulfonic stilbene

1979

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Bicarbonate is transferred across the serosal (S) membrane of the epithelial cells of the turtle bladder in two directions. Cellular HCO3- generated behind the H+ pump moves this membrane into the serosal solution. This efflux of HCO3- is inhibited by SITS (4-isothiocyano-4'-acetamido-2,2'-disulfonic stilbene). When HCO3- is added to the serosal solution it is transported across the epithelium in exchange for absorbed Cl-. This secretory HCO3- flow traverses the serosal cell membrane in the opposite direction. In this study the effects of serosal addition of 5 x 10(-4) M SITS on HCO3- secretion and Cl- absorption were examined. The rate of H+ secretion was brought to zero by an opposing pH gradient, and 20 mM HCO3- was added to S. HCO3- secretion, measured by pH stat titration, was equivalent to the increase in M leads to S Cl- flux after HCO3- addition. Neither the S leads to M flux of HCO3- nor the M leads to S flux of Cl- were affected by SITS. In the absence of electrochemical gradients, net Cl- absorption was observed only in the presence of HCO3- in the media; under such conditions, unidirectional and net fluxes of Cl- were not altered by serosal or mucosal SITS. H+ secretion, however, measured simultaneously as the short-circuit current in ouabain-treated bladders decreased markedly after serosal SITS. The inhibition of the efflux of HCO3- in series with the H+ pump and the failure of SITS to affect HCO3- secretion and Cl- absorption suggest that the epithelium contains at least two types of transport systems for bicarbonate in the serosal membrane.

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Inhibition of the Bicarbonate Exit Step in Urinary Acidification by a Disulfonic Stilbene

Cited by 60 publications

References 21 publications

Effects of Anion-Transport Inhibitors on NaCl Reabsorption in the Rat Superficial Proximal Convoluted Tubule

Effects of Anion-Transport Inhibitors on NaCl Reabsorption in the Rat Superficial Proximal Convoluted Tubule

Marginal Effect of Changes in Acid-Base Status in vitro on Rheogenic H<sup>+</sup> and HCO<sup>-</sup><sub>3</sub> Secretion in Turtle Urinary Bladder

Pathways for bicarbonate transfer across the serosal membrane of turtle urinary bladder: Studies with a disulfonic stilbene

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