Depression of Chloride Transport by Carbonic Anhydrase Inhibitors in the Absence of Carbonic Anhydrase

Kitahara, S; Fox, Karl R.; Hogben, C. Adrian M.

doi:10.1038/214836a0

Cited by 45 publications

(15 citation statements)

References 9 publications

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“…Irrespective of such general criticism, it does seem likely that metabolic carbon dioxide will accumulate in the interstitial fluid of this preparation, despite vigorous stirring of the bathing fluid, and thus be more readily available as a source ofsecretary bicarbonate. This would explain why the bicarbonate concentration in pancreatic juice secreted during acetate-substitution was slightly higher in the rabbit (9 mM) than in the cat (5-7 mM), and why bicarbonate secretion from the rabbit gland suspended in fluid 'free' of carbon dioxide or bicarbonate (and (Case et al 1970, and this (Kitahara, Fox & Hogben, 1967), and presumably could act in this way elsewhere. In view of these two observations, it was reassuring to observe that acetazolamide continued to inhibit secretion on the absence of chloride, but not during bicarbonate substitution.…”

Section: Discussionmentioning

confidence: 98%

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

Case¹,

Hotz²,

Hutson³

et al. 1979

The Journal of Physiology

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SUMMARY1. The effect of replacing extracellular bicarbonate and chloride by other anions on the volume and composition of secretin-stimulated pancreatic juice has been analysed in the isolated, perfused cat pancreas.2. The anions of some aliphatic carboxylic acids were able partially to substitute for bicarbonate in sustaining pancreatic secretion. The order of effectiveness was: acetate > propionate > butyrate > formate.3. The rate of secretion in the presence of 25 mM-acetate was 42 % of that achieved with 25 mM-bicarbonate. The concentration of acetate in the secretion varied with flow rate, reaching a maximum of 120 mm at high flow rates and declining at lower flow rates, with reciprocal changes in chloride concentration. Bicarbonate was always present in the secretion at a concentration of 5-7 mM. 4. Inorganic anions were able totally or partially to substitute for chloride in sustaining secretion. In relation to chloride, their degree of effectiveness was: chloride -bromide = or > nitrate > iodide > sulphate > methyl sulphate > isethionate. Those anions which had no effect on secretion rate (i.e. bromide and nitrate) also had no effect on the bicarbonate concentration of the secretion and themselves appeared in the secretion in place of chloride. Those anions which inhibited secretion increased the bicarbonate concentration in the secretion in proportion to the degree of inhibition they caused (i.e. the increase was greatest with isethionate).5. When perfusate chloride was only partially replaced by bromide or iodide the ratios of chloride: bromide and chloride: iodide in the secretion were approximately equal to those in the perfusate.6. The carbonic anhydrase inhibitor acetazolamide reduced secretary rate and bicarbonate concentration when added to normal perfusion fluid or chloridesubstituted fluids, but had no effect following replacement of perfusate bicarbonate by acetate.7. These observations illustrate that an extracellular source of permeant anions is

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Section: Discussionmentioning

confidence: 98%

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

Case¹,

Hotz²,

Hutson³

et al. 1979

The Journal of Physiology

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“…These experiments cannot be used as conclusive proof for the model, however, since it is possible that acetazolamide exerts its effect directly on sodium and chloride absorption and not via inhibition of carbonic anhydrase (10).…”

Section: Nonelectrogenic Nature Of Ileal Ion Transport In Manmentioning

confidence: 94%

Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum

Turnberg¹,

Bieberdorf²,

Morawski³

et al. 1970

J. Clin. Invest.

346

153

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A B S T R A C T Using a triple-lumen constant perfusion system, the following observations were made in normal subjects. First, chloride, bicarbonate, and sodium were found to exhibit net movement across ileal mucosa against electrochemical gradients. Second, during perfusion with a balanced electrolyte solution simulating plasma, the ileum generally absorbed, but sometimes secreted fluid. A reciprocal net movement of chloride and bicarbonate was noted when sodium movement was zero. Increasing rates of sodium absorption were associated with decreasing bicarbonate secretion rates and finally bicarbonate absorption. Even when bicarbonate was absorbed ileal contents were alkalinized (by contraction of luminal volume). Third, net chloride movement was found to be sensitive to bicarbonate concentration in ileal fluid. For instance, chloride was absorbed from solutions containing 14 or 44 mEq/liter of bicarbonate, but was secreted when ileal fluid contained 87 mEq/liter of bicarbonate. Fourth, when chloridefree (sulfate) solutions were infused, the ileum absorbed sodium bicarbonate and the ileal contents were acidified. Fifth, when plasma-like solutions were infused, the potential difference (PD) between skin and ileal lumen was near zero and did not change when chloride was replaced by sulfate in the perfusion solution.These results suggest that ileal electrolyte transport occurs via a simultaneous double exchange, Cl/HCOs and Na/H. In this model neither the anion nor the cation exchange causes net ion movement; net movement results from the chemical reaction between hydrogen and bicarbonate. No other unitary model explains all of the following observations: (a) human ileal transport in vivo is essentially nonelectrogenic even though Na, Cl, and HCO3 are transported against electrochemical Dr. Turnberg's present address is Manchester Royal Infirmary, Oxford Road, Manchester 13, England.

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“…The administration of carbonic anhydrase inhibitors has been shown to inhibit chloride transport in a number of different tissues. For example, chloride transport has been inhibited in the frog gastric mucosa (14) and turtle bladder (15), tissues which contain carbonic anhydrase (14,16) and the bullfrog cornea which is thought to be devoid of carbonic anhydrase (17). In addition, Turnberg, Bieberdorf, Morawski, and Fordtran recently have observed acetazolamide administration to inhibit sodium and chloride reabsorption in the human ileum (18), a tissue which possibly contains carbonic anhydrase (19,20).…”

Section: Figurementioning

confidence: 99%

The Influence of the Carbonic Anhydrase Inhibitor, Benzolamide (CL-11,366), on the Reabsorption of Chloride, Sodium, and Bicarbonate in the Proximal Tubule of the Rat

Kunau¹

1972

J. Clin. Invest.

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Depression of Chloride Transport by Carbonic Anhydrase Inhibitors in the Absence of Carbonic Anhydrase

Cited by 45 publications

References 9 publications

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum

The Influence of the Carbonic Anhydrase Inhibitor, Benzolamide (CL-11,366), on the Reabsorption of Chloride, Sodium, and Bicarbonate in the Proximal Tubule of the Rat

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