Actions of vasopressin and aldosterone on the toad bladder: inhibition by ethacrynic acid.

Abstract

SUMMARY Ethacrynic acid inhibited short-circuit current (SCC, Na transport) across the toad bladder. Some structural analogues had similar effects and their potency varied with their ability to combine with SH groups. The Na-K ATPase inhibitor ouabain was more effective than ethacrynic acid and its action and that of ethacrynic acid was additive. The natriferic and hydro-osmotic effects of vasopressin were inhibited by ethacrynic acid (10−5 and 10−4m); the antagonism was competitive at 10− and 10−4 m (but not at 10−3 m). Certain analogues of ethacrynic acid also exhibited this effect but it was not clearly related to their SH-combining ability. The natriferic and hydro-osmotic effects of caffeine and cyclic AMP were not changed by 10−4 m-ethacrynic acid. Ethacrynic acid (10−4 m), which does not affect basal sodium transport in bladders pretreated for studying the action of aldosterone, prevented the initiation of the increase in sodium transport by aldosterone but was without effect when added to a toad bladder already under the influence of aldosterone. This suggests that ethacrynic acid interferes with metabolic processes underlying the action of aldosterone. Dihydroethacrynic acid which has no SH-binding activity was without effect.