1. Experiments were designed to establish the relationship between renal gluconeogenesis and sodium transport. Six inhibitors of gluconeogenesis, with different sites of action, were tested in the isolated perfused rat kidney in which renal function, and in particular Na + reabsorption, was followed. 2. In kidneys from fed or starved rats specific inhibitors of gluconeogenesis neither inhibited nor stimulated Na + reabsorption; gluconeogenesis and sodium reabsorption are therefore independent of one another under these conditions. 3. Inhibitors of transaminase or malic dehydrogenase inhibited gluconeogenesis from lactate and pyruvate respectively; the transaminase inhibitor significantly inhibited oxidation of lactate and glucose. 4. Sodium reabsorption was inhibited by a transaminase inhibitor when glucose or lactate was the sole substrate, and by inhibition of malic dehydrogenase when pyruvate was the substrate. 5. These results indicate that the malate-aspartate shuttle controls Na + reabsorption in the intact kidney by regulating substrate oxidation (and the provision of energy) rather than by any direct involvement of gluconeogenesis in Na + transport.
1. The metabolism of [ 3 H]paracetamol has been studied in the perfused rat kidney. Seventy-four per cent of filtered paracetamol was reabsorbed. Paracetamol appeared in the urine; 90%was unaltered but 10%appeared as metabolites: the glucuronide, sulphate, mercapturic acid and cysteine conjugates. 2. At concentrations of paracetamol of 1–3 mmol/l no impairment of renal physiological function was observed. 3. The presence of the mercapturic acid and cysteine conjugates in the urine demonstrates the capacity of the kidney for oxidative metabolism of paracetamol and hence the formation of potentially toxic intermediates.