Indirect Na+ dependency of urate and p-aminohippurate transport in pig basolateral membrane vesicles

Membrane vesicles were used to study the basolateral transport of urate and p-aminohippurate (PAH) in the proximal tubule of the pig kidney. Consistent with a cooperation between a Na(+)-2-oxoglutarate cotransporter and a 2-oxoglutarate-urate or a 2-oxoglutarate-PAH exchanger, urate and PAH uptakes were stimulated in presence of extravesicular 2-oxoglutarate when an inwardly directed Na+ gradient was applied. Both transports exhibited, however, different characteristics. The optimal 2-oxoglutarate concentration for stimulating uptakes was 10 microM for PAH and 150 microM for urate. Extravesicular chloride was required to observe a stimulation of PAH uptake but not of urate uptake. Transports of both PAH and urate exhibited different affinity sequences for various organic anions. Stimulated PAH uptake was inhibited by probenecid greater than cold PAH greater than urate = pyrazinoate greater than lactate, whereas stimulated urate uptake was inhibited by probenecid greater than cold urate greater than PAH and not by pyrazinoate or lactate. These results are consistent with independent transport processes for urate and PAH in pig basolateral membrane vesicles, both being indirectly driven by an inwardly directed Na+ gradient.