WEAK ORGANIC-ACID UPTAKE IN RAT RENAL TUBULES IN-VITRO - STIMULATION BY PENT-4-ENOIC ACID

A hypoglycemic agent, pent-dienoic 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 produ ction from pyruvate (but not lactate or endogenous substrates) by rat renal cortex fragment suspension. The stimulation of the fluorescein u ptake was not observed in a low Nat medium. Maleate (0.1-1.0 mM) and C d2+ (0.1 mM), known similarly to 4-PA to induce the renal Fanconi synd rome, also stimulated the fluorescein uptake in the Na-dependent manne r. Both 4-PA and Cd2+ and maleate elevated intracellular content of al pha-ketoglutarate and increased ammonia formation from endogenous subs trates in the suspension of the rat renal cortex fragments. The stimul atory 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 fluo rescein uptake in the exchange for the cytoplasmic dicarboxylate. (C) 1997 Elsevier Science Inc.