The site of action of the diuretic ethacrynic acid on rat kidney and liver tissue

Poat, Peter C.; Poat, Judith A.; Munday, K. A.

doi:10.1016/0010-4035(70)90064-9

Cited by 15 publications

(8 citation statements)

References 14 publications

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“…Both pumps may be concerned in transepithelial sodium transport. Part of the evidence for this second pump is, however, based on the results of experiments with the diuretic ethacrynic acid, the interpretation of which remains controversial, for some workers (Macknight, 1969;Poat, Poat & Munday, 1970;Epstein, 1972) claim that the effects of ethacrynic acid reflect a nonspecific interference with cellular metabolism rather than a specific direct inhibition of a sodium pump.…”

Section: Relationships Between Transepithelial Sodium Transport Cellmentioning

confidence: 99%

Some effects of ouabain on cellular ions and water in epithelial cells of toad urinary bladder

1975

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Transepithelial sodium transport was virtually abolished when toad urinary hemibladders, mounted in chambers and short-circuited, were exposed on their serosal surface to ouabain, 10-2 M,for 60 minutes. Epithelial cells scraped from such hemibladders gained sodium and lost an equal quantity of potassium when compared with controls not exposed to cardiac glycoside. Their total cellular cation content, chloride content and water content were unchanged. Experiments in which 24-Na, amiloride, or sodium-free mucosal solutions were used, revealed that a large, though variable, percentage of the sodium gained by cells exposed to oubain, came from the mucosal medium, a finding consistent with the model of passive sodium entry from the mucosal medium followed by active sodium extrusion to the serosa. The oubain-insensitive maintenance of cellular volume which was observed did not depend upon transepithelial sodium transport which had been virtually completely inhibited by ouabain. Neither did the maintenance of a normal cellular potassium content depend upon transepithelial sodium transport, for cellular potassium was unaffected when the mucosal medium was sodium-free or when it contained sufficient amiloride, 10-3 M, to virtually abolish such transport.

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Section: Relationships Between Transepithelial Sodium Transport Cellmentioning

confidence: 99%

Some effects of ouabain on cellular ions and water in epithelial cells of toad urinary bladder

1975

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“…As Shami and Radde (6,7 ) and this study demonstrate, the Ca2+-ATPases also are inhibited by ethacrynic acid. This action may reflect a nonspecific effect of ethacrynic acid, perhaps related to the metabolic effects of this compound noted in other tissues (20)(21)(22)(23). Also suhfhydryl group inhibitors, e.g., N-ethylmaleimide, did not block the binding or up- take of ethacrynic acid in the rabbit renal cortex (24).…”

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Evidence for Mg2+-Dependent, Na+ + K+-Activated ATPase and Ca2+-ATPase in the Human Term Placenta

Miller

Berndt

1973

Experimental Biology and Medicine

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“…Alternatively, the effects of ethacrynic acid on renal slices have been ascribed to an inhibition of cellular metabolism together with an increased membrane permeability (Macknight, 1969;Poat, Poat & Munday, 1970;Epstein, 1972). It was therefore of interest to examine the effects of ethacrynic acid on guinea-pig cortical slices incubated in choline Ringer (Table 7), for in the absence of medium sodium the inhibition by ethacrynic acid of a specific sodium pump should be without effect on cellular volume.…”

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Effects of replacing medium sodium by choline, caesium, or rubidium, on water and ion contents of renal cortical slices

Hughes

Macknight

1977

The Journal of Physiology

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SUMMARY1. Renal cortical slices from rat, rabbit, and guinea-pig were incubated in media in which choline, caesium or rubidium replaced sodium.2. Slices of rabbit and guinea-pig renal cortex incubated in oxygenated choline Ringer decreased in volume initially and did not swell over 3 hr at 250 C. There was a steady loss of potassium. Inhibition of metabolism (N2 +1 mM iodoacetamide) caused some swelling. Ouabain, 10 mm, in choline Ringer affected neither loss of potassium nor tissue water content.3. Slices of rat renal cortex similarly incubated in choline Ringer swelled over 3 hr at 250 C whether or not metabolism was inhibited; ouabain (15 mM) affected neither tissue potassium loss nor tissue water content.4. Incubation in choline Ringer containing either 0-2 mm p-chloromercuribenzoic acid, or 1 mm ethacrynic acid increased the tissue water content of guinea-pig renal cortical slices.5. Depletion of cellular potassium (by preliminary incubation in oxygenated potassium-free sodium Ringer with 10 mm ouabain at 300 C) resulted in increased tissue water content when rabbit renal cortical slices were subsequently incubated in oxygenated choline Ringer at 250 C for 3 hr.6. There was no evidence of energy-dependent extrusion of water or ions from either equilibrated rat or rabbit renal cortical slices leached at 0.50 C and then reincubated at 250 C in choline Ringer.7. Rat and guinea-pig renal cortical slices leached at 0.50 C and reincubated at 250 C swelled in rubidium Ringer and in caesium Ringer. There was no evidence of energy-dependent water or ion extrusion when metabolism was restored after leaching in either of these media. Metabolizing rat slices but not guinea-pig slices swelled faster than slices whose metabolism was inhibited. P. M. HUGHES AND A. D. C. MACKNIGHT 8. These results lend no support to the mechano-chemical hypothesis which ascribes cellular volume regulation to a contractile mechanism squeezing isotonic extracellular fluid from the cells. Instead it is suggested that cellular water content in these experiments reflects the balance between the rate of loss of potassium (and chloride) from the cells and the rate of uptake of extracellular cation (and chloride) into the cells -these rates reflecting both the electrochemical potential gradients of the ions and membrane permeability to them. The implications in relation to the hypothesis of ouabain-insensitive cellular volume regulation are discussed.

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The site of action of the diuretic ethacrynic acid on rat kidney and liver tissue

Cited by 15 publications

References 14 publications

Some effects of ouabain on cellular ions and water in epithelial cells of toad urinary bladder

Some effects of ouabain on cellular ions and water in epithelial cells of toad urinary bladder

Evidence for Mg2+-Dependent, Na+ + K+-Activated ATPase and Ca2+-ATPase in the Human Term Placenta

Effects of replacing medium sodium by choline, caesium, or rubidium, on water and ion contents of renal cortical slices

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