Werner D, Roch-Ramel F
Institut de Pharmacologie et de Toxicologie, Université de Lausanne, Switzerland.
Am J Physiol. 1991 Aug;261(2 Pt 2):F265-72. doi: 10.1152/ajprenal.1991.261.2.F265.
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.
膜囊泡被用于研究猪肾近端小管中尿酸盐和对氨基马尿酸(PAH)的基底外侧转运。与Na⁺-2-氧代戊二酸共转运体和2-氧代戊二酸-尿酸盐或2-氧代戊二酸-PAH交换体之间的协同作用一致,当施加内向型Na⁺梯度时,在囊泡外2-氧代戊二酸存在的情况下,尿酸盐和PAH的摄取受到刺激。然而,两种转运表现出不同的特征。刺激摄取的最佳2-氧代戊二酸浓度对于PAH为10微摩尔,对于尿酸盐为150微摩尔。需要囊泡外氯离子来观察PAH摄取的刺激,但不需要观察尿酸盐摄取的刺激。PAH和尿酸盐的转运对各种有机阴离子表现出不同的亲和力序列。刺激的PAH摄取被丙磺舒抑制的程度大于冷PAH大于尿酸盐 = 吡嗪酸盐大于乳酸盐,而刺激的尿酸盐摄取被丙磺舒抑制的程度大于冷尿酸盐大于PAH,且不受吡嗪酸盐或乳酸盐抑制。这些结果与猪基底外侧膜囊泡中尿酸盐和PAH的独立转运过程一致,两者均由内向型Na⁺梯度间接驱动。