The effects of ethacrynic acid on active transport of sugars and ions and on other metabolic processes in rabbit kidney cortex

Abstract

The effects of ethacrynic acid and several of its chemical analogues on the active transport of sugars and electrolytes, on cell volume, O 2 utilization, and tissue content of ATP were studied in slices of rabbit kidney cortex. 1. 1. Incubation of the tissues in 0.5–3.0 mM ethacrynic acid sharply inhibited both Na +-dependent and Na +-dependent and Na +-independent active transport of sugars and the maintenance of normal tissue electrolyte distribution; water content was inhibited in the same range of concentrations. 2. 2. The magnitudes of the above inhibitory effects were functions of both the time that the tissue was exposed to the inhibitor and the medium concentration of the inhibitor. 3. 3. Incubation of rabbit kidney cortex slices with four chemical analogues of ethacrynic acid, characterized by widely varying sulfhydryl reactivity, in the same concentration ranges revealed qualitatively similar effects on the above-mentioned transport processes. Hence, a structure-function relationship between sulfhydryl-reacting structure and inhibitory effects of ethacrynic acid and its analogues was not observed. 4. 4. Ethacrynic acid and its analogues diminished O 2 uptake of the tissue in both Na +-containing and Na +-free media. The inhibition of O 2 uptake was, therefore, not merely reflective of ethacrynic acid-induced diminished energy requirements for Na + pumping. 5. 5. Rapid diminution of tissue ATP content occurred during tissue incubation with ethacrynic acid. 6. 6. The results presented are interpreted as indicating that ethacrynic acid exerts inhibitory effects on several levels of cell metabolism and thus is not a specific inhibitor of individual active transport processes.