Role of the Malate-Aspartate Shuttle in Renal Sodium Transport in the Rat

Abstract

Experiments were designed to establish the relationship between renal gluconeogenesis and Na 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. In kidneys from fed or starved rats specific inhibitors of gluconeogenesis neither inhibited nor stimulated Na+ reabsorption; gluconeogenesis and Na reabsorption are therefore independent of one another under these conditions. Inhibitors of transaminase or malic dehydrogenase inhibited gluconeogenesis from lactate and pyruvate, respectively; the transaminase inhibitor significantly inhibited oxidation of lactate and glucose. 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. 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.