Effect of diuretics on ADP incorporation in kidney mitochondria

The effect of diuretics on incorporation of ADP in mitochondria isolated from rabbit renal cortex and medulla was examined. Inhibition of incorporation of [ ¹⁴C]ADP into both types of mitochondria was observed following pretreatment with furosemide, ethacrynic acid and meralluride at high drug concentrations (7.5 X 10 ^-4 M furosemide and ethacrynic acid, 6.4 X 10 ^-3 M meralluride). At lower concentrations (7.5 X 10 ^-5 M furosemide and ethacrynic acid, 6.4 X 10 ^-4 M meralluride), only entry of ADP in medullary mitochondria was inhibited. Chlorothiazide, 1.7 X 10 ^-3 M, did not inhibit incorporation of ADP into either mitochondrial preparation. Atractyloside, a classic inhibitor of ADP-ATP exchange, showed inhibition in both preparations. Furosemide, injected in vivo, inhibited incorporation of ADP into medullary but not cortical mitochondria. These results are consistent with the possibility that loop diuretics may reduce tubular sodium reabsorption by inhibiting ADP-ATP exchange across the mitochondrial membrane, thereby depriving active transport processes of ATP. The differential action on cortical and medullary mitochondria by loop diuretics is consistent with their predominant site of action in the tubule and with the different morphologic characteristics of both types of mitochondria.