Metabolic inhibitors: effects on metabolism and transport in the proximal tubule

Abstract

The effects of the metabolic inhibitors rotenone and antimycin A on oxidative metabolism and transport were examined in the proximal renal tubule of the rabbit. Measurements of O2 consumption rate (QO2), cellular ATP content, and mitochondrial NAD redox state were made in suspensions of renal cortical tubules. Parallel experiments were conducted in isolated perfused proximal convoluted tubules to measure the absorption rates of fluid (Jv), phosphate .**GRAPHIC**. and glucose .**GRAPHIC**. Rotenone and antimycin A, at doses (10-6 M) that maximally inhibited mitochondrial oxidative phosphorylation, apparently abolished net fluid and phosphate absorption and nearly eliminated net glucose transport. Partial inhibition of oxidative metabolism with 10-7 M rotenone caused proportional reductions in QO2, ATP content and Jv; .**GRAPHIC**. was reduced more markedly than either Jv or .**GRAPHIC**. Apparently, rotenone and antimycin A inhibit the Na-dependent transport of fluid, phosphate and glucose by blocking mitochondrial ATP production. The inhibition of mitochondrial oxidative metabolism and the inhibition of net Na transport are closely correlated.