STIMULATORY EFFECT OF ETHANOL ON WEAK ORGANIC-ACID UPTAKE IN RAT RENAL TUBULES

Ethanol at relatively low concentrations (10-40 mM) significantly stim ulated the uphill uptake of a weak organic acid, fluorescein, in the s uperficial proximal tubules of rat renal cortex slices, but it did not affect the rate of glucose production from lactate or pyruvate in rat renal cortex fragment suspension. In a low Na+ medium, ethanol failed to stimulate fluorescein uptake, although under the conditions employ ed in the present study, the baseline weak organic acid uptake was not dependent on external Na+. The stimulation of fluorescein uptake by e thanol (20 mM) was abolished by an inhibitor of alcohol dehydrogenase (EC 1.1.1.1), pyrazole (1 mM), or an inhibitor of aldehyde dehydrogena se (EC 1.2.1.3), cyanamide (0.3 mM), suggesting that oxidation of etha nol mediated its effect on the uptake. Among gluconeogenesis inhibitor s tested, only D-malate (2 mM) abolished the stimulatory effect of eth anol, while the rest either did not affect (quinolinate) or even sligh tly augmented (alpha-cyano-4-hydroxycinnamate and phenylpyruvate) it. The effect of ethanol was markedly increased by an inhibitor of the tr icarboxylic acid cycle, fluoroacetate. It was concluded that the stimu lation by ethanol of weak organic acid uptake in rat renal tubules was mediated by the production of acetate.