Relation between cell na extrusion and transtubular absorption in the perfused toad kidney: the effect of K, ouabain and ethacrynic acid

Whittembury, Guillermo; Fishman, Jerry H.

doi:10.1007/bf00592080

Cited by 67 publications

(10 citation statements)

References 35 publications

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“…This is unlikely, however. Except at extremely slow perfusion rates (27), the isolated collecting tubule net fluid absorption is negligible in the absence of an osmotic gradient, with or without ADH present (16). Moreover, this study shows that, in the absence of ADH ethacrynic acid does not nmodify water absorption.…”

Section: Discussionmentioning

confidence: 63%

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Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Abramow¹

1974

J. Clin. Invest.

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A B STRACT Effects of the diuretic ethacrynic acid on osmotic water permeability were investigated in the isolated perfused collecting tubule of the rabbit kidney.The base-line water permeability of the collecting tubule was not affected when the drug (10-'M) alone was added to the bathing medium. Vasopressin alone in the bathing medium (2, 5 AU/ml) elicited a significant increase in osmotic water absorption. With vasopressin kept in the bathing medium, the addition of 10-'M ethacrynic acid depressed the hydro-osmotic effect of vasopressin by 50%. This inhibitory effect of low concentrations of ethacrynic acid could be surmounted by high, supramaximal dosage levels of vasopressin.When 10-4M ethacrynic acid was added to the bathing medium before vasopressin, the hydro-osmotic effect of vasopressin and the diuretic in combination was insignificant.Dibutyryl adenosine 3'5'-monophosphate (10-4-10-'M) alone in the bathing medium significantly increased baseline osmotic water flow, mimicing the effect of antidiuretic hormone. When ethacrynic acid was added together with the nucleotide, the permeability remained at the same high level. Theophylline, like the nucleotide and vasopressin, produced a significant hydro-osmotic effect. The magnitude of this responise was not affected by further addition of ethacrynic acid (10-4`\).It was concluded that ethacrynic acid is an antagonist of antidiuretic hormone. The antagonism probably occurs at the level of the receptor site of the hormone on the peritubular membrane. Antagonism to circulating antidiuretic hormone may therefore be one of the factors involved in the loss of renal concentrating ability brought about by ethacrynic acid diuresis.

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Section: Discussionmentioning

confidence: 63%

“…Ethacrynic acid interferes with sodium chloride transport in a variety of tissues (24)(25)(26)(27). The inhibitory efaTheophylline indeed inhibits cyclic nucleotide phosphodiesterases, thereby permitting accumulation of intracellular cAMP through basal activity of adenyl cyclase (18,19).…”

Section: Discussionmentioning

confidence: 99%

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Abramow¹

1974

J. Clin. Invest.

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“…In favour of this concept is the observation that, during partial isosmotic replacement of perfusate sodium with sucrose, large concentration gradients of sodium can be established between secretion and perfusate (Case et al 1968a) and that the gland contains Na+, K+-ATPase (Ridderstap & Bonting, 1969a, b). The immediate inhibition of secretion by ouabain, frusimide and ethacrinic acid also supports a role for a sodium pump although ethacrinic acid could exert its action either on a second sodium pump (Whittembury & Fishman, 1969) or on sulphydryl groups known to be present on the surface of the secretary cell (Wizemann, Schulz & Simon, 1973).…”

Section: R M Case and T Scratcherd Discussionmentioning

confidence: 78%

The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na⁺, K⁺‐ATPase activity

Case¹,

Scratcherd²

1974

The Journal of Physiology

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SUMMARY1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin.2. Under isosmolal conditions, when perfusate sodium chloride was replaced by sucrose, sodium secretion and potassium secretion were directly related to perfusate sodium concentration, [Na] The concentration of potassium in the secretion was almost identical with that in the perfusate over the whole concentration range.6. Replacement of perfusate sodium by lithium reduced the volume of secretion, though a small secretion was maintained even in the complete absence of sodium. The concentration of lithium in the secretion was generally slightly greater than that in the perfusate.7. Omission of potassium from the perfusate reduced secretion by about 65 %. Rubidium was a complete substitute for potassium; caesium was not.

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“…DISCUSSION Ethacrynic acid, a potent sulfhydryl inhibitor and diuretic agent in humans (13), has been shown to interfere with active cation transport in renal tubules (14), kidney slices (15,16), toad bladder (17), smooth muscle (18), striated muscle (19), toad oocytes (20), and human erythrocytes (3,4,(20)(21)(22)(23). As such it appears to have widespread inhibitory potency for active cation transport.…”

Section: Resultsmentioning

confidence: 99%

The effects of transport inhibitors on sodium outflux and influx in red blood cells: evidence for exchange diffusion

Dünn¹

1970

J. Clin. Invest.

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A iB S T R A C T Active sodium transport (outflux or efflux) in red blood cells generally has been measured by assessing the amount of outflux inhibited by digitalis glycosides (outflux-fraction I). The presence of a ouabain-uninhibited sodium outflux (outflux-fraction II) attributable either to a second active transport mechanism or to exchange diffusion has been the subject of recent investigations. In the present study a variety of transport inhibitors, including ouabain, ethacrynic acid, furosemide, oligomycin, and amiloride, were studied for their effects on these components of sodium transport in RBC.In the presence of ouabain both ethacrynic acid and furosemide exerted similar effects on sodium outflux, inhibiting approximately 0.5 mmoles/L of cells per hr. This component of sodium outflux has been called outflux-fraction II. Ethacrynic acid showed no inhibitory potency when ouabain and furosemide were present, thereby suggesting that the same outflux component (fraction II) was affected by ethacrynic acid and by furosemide. In addition, furosemide reduced sodium influx to the same extent that it reduced sodium outflux. Outflux-fraction II, as defined by furosemide, did not contribute a net sodium outflux. These results of sodium outflux and influx experiments confirm the existence of a transport pathway which does not contribute to net flux and which fits the definition of exchange diffusion.

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Relation between cell na extrusion and transtubular absorption in the perfused toad kidney: the effect of K, ouabain and ethacrynic acid

Cited by 67 publications

References 35 publications

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na⁺, K⁺‐ATPase activity

The effects of transport inhibitors on sodium outflux and influx in red blood cells: evidence for exchange diffusion

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Relation between cell na extrusion and transtubular absorption in the perfused toad kidney: the effect of K, ouabain and ethacrynic acid

Cited by 67 publications

References 35 publications

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

Effects of Ethacrynic Acid on the Isolated Collecting Tubule

The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na+, K+‐ATPase activity

The effects of transport inhibitors on sodium outflux and influx in red blood cells: evidence for exchange diffusion

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The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na⁺, K⁺‐ATPase activity