Effect of lithium on renal transport and utilization of alpha- ketoglutarate in the rat

B Ferrier, M Martin and G Baverel

Institut National de la Sante et de la Recherche Medicale (U 80), Centre National de la Recherche Scientifique (UA 1177), Lyon, France.

Experiments were carried out in the intact functioning rat kidney to study the effect of lithium on both the renal transport of alpha- ketoglutarate (alpha-KG) along the nephron by micropuncture techniques and the renal uptake and peritubular transport of alpha-KG by measuring the renal blood flow, the urinary flow and the rate of renal alpha-KG delivery, filtration, reabsorption or secretion and excretion. At endogenous plasma alpha-KG concentration, 2.3 mM plasma lithium caused an increase in the fractional excretion of alpha-KG, whereas 4.6 mM plasma lithium led to a net secretion of alpha-KG. The micropuncture data indicate that this secretion occurred between the late proximal and the distal tubule, i.e., in the pars recta and/or in the loop of Henle. When plasma alpha-KG concentration was elevated, the two doses of lithium used inhibited the reabsorption of alpha-KG both in the proximal tubule and in the pars recta and/or the loop of Henle. Renal arteriovenous measurements reveal that, at low plasma alpha-KG concentrations, lithium caused a significant decrease in both the renal uptake of alpha-KG and the peritubular transport of this organic anion. These results suggest that the alpha-KG secreted in the pars recta and/or the loop of Henle was synthesized within the renal cells of the latter segments and not transported from the blood to the tubular lumen. At higher plasma alpha-KG concentrations, both the peritubular transport and the renal reabsorption were reduced by lithium.

Volume 253, Issue 1, pp. 321-327, 04/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics