Weak organic acid uptake in rat renal tubules in vitro: stimulation by pent-4-enoic acid.

A hypoglycemic agent, pent-4-enoic acid (4-PA; 0.1-1.0 mM), stimulated baseline uptake of a weak organic anion, fluorescein, in superficial proximal tubules of rat kidney and inhibited the rate of glucose production from pyruvate (but not lactate or endogenous substrates) by rat renal cortex fragment suspension. The stimulation of the fluorescein uptake was not observed in a low Na+ medium. Maleate (0.1-1.0 mM) and Cd2+ (0.1 mM), known similarly to 4-PA to induce the renal Fanconi syndrome, also stimulated the fluorescein uptake in the Na-dependent manner. Both 4-PA and Cd2+ and maleate elevated intracellular content of alpha-ketoglutarate and increased ammonia formation from endogenous substrates in the suspension of the rat renal cortex fragments. The stimulatory effects of 4-PA, maleate and Cd2+ on the fluorescein uptake were markedly attenuated by LiCl (5 mM), suggesting that the Na-coupled re-uptake of alpha-ketoglutarate is involved in energization of the fluorescein uptake in the exchange for the cytoplasmic dicarboxylate.