Abstract
Cellular effects of ethacrynic acid were examined in the rabbit and rat kidney. Emphasis was placed on levels of the compound in vitro lower than those employed in earlier studies. In the present study in vitro, ethacrynic acid is without effect on sodium-potassium-dependent adenosine triphosphatase (ATPase) activity. When 0.1 mM ethacrynic acid is incubated with rabbit kidney cortex slices, it inhibits the maintenance of intracellular potassium but has no effect on cellular respiration or cell volume. Ethacrynic acid (0.05 mM) inhibits the respiration of isolated mitochondria and suppresses membrane ATPase stimulation of mitochondrial respiration. Ethacrynic acid administered in vivo at a dose sufficient to elicit a diuretic response does not affect kidney mitochondrial respiration or inhibit the sodium-potassium-dependent ATPase activity. Ethacrynic acid labeled with carbon-14 localizes in part in the kidney plasma membrane. About 90 per cent of the plasma membrane-bound ethacrynic acid is found in association with proteins comprising the low molecular weight fraction. The compound is not bound significantly to cell membrane macromolecules associated with the ATPase system.
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