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

Abstract

This study examined the effects of the metabolic inhibitors rotenone and antimycin A on oxidative metabolism and transport in the proximal renal tubule of the rabbit. Measurements of oxygen 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 (JlbPO4), and glucose (JlbGlc). The results indicate that rotenone and antimycin A, at doses (10(-6) M) that maximally inhibited mitochondrial oxidative phosphorylation, 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; however, JlbPO4 was reduced more markedly than either Jv or JlbGlc. We conclude that rotenone and antimycin A inhibit the sodium-dependent transport of fluid, phosphate, and glucose by blocking mitochondrial ATP production. Furthermore, the inhibition of mitochondrial oxidative metabolism and the inhibition of net sodium transport are closely correlated.