Inhibition of mitochondrial Mg2+ ATPase activity in isolated perfused rat liver by kepone.

Hepatic mitochondria Mg²⁺ ATPase (MATPase) activity was determined in isolated perfused rat liver preparations. Perfusion for 1–4 hr with 30% rat blood did not affect either the native or DNP (10^?4 M)-stimulated MATPase activity. Mitochondrial preparations obtained from perfused livers were sensitive to added kepone: first, addition of kepone (10^?6M) resulted in total abolishment of DNP-stimulated MATPase activity; second, over and beyond the abolishment of DNP-stimulated activity, part of the native MATPase activity was also inhibited by kepone (10^?6M). Furthermore, a higher concentration of kepone (10^?5 M) inhibited the native MATPase activity in a dose-related manner. Liver perfusion with 10^?4 M kepone in the blood perfusate resulted in a similar abolishment of DNP-stimulated. as well as inhibition of native, MATPase activity. The requirement for a higher concentration of kepone in the perfusion system is because of the partial loss of intracellular kepone from the liver into the 9000 g supernatant fraction which would have been otherwise available for the inhibition of MATPase activity in the intact liver. These results suggest that interference of energy metabolism in the liver may bear a cause effect relationship to the previously reported kepone-induced impairment of biliary excretory function.