Shimada H, Moewes B, Burckhardt G
Max-Planck-Institut für Biophysik, Frankfurt/Main, Federal Republic of Germany.
Am J Physiol. 1987 Nov;253(5 Pt 2):F795-801. doi: 10.1152/ajprenal.1987.253.5.F795.
Experiments with basolateral membrane vesicles prepared from rat kidney cortex were performed to study the mechanism by which p-aminohippuric acid (PAH) is taken up across the contraluminal membrane and is concentrated in proximal tubule cells. An inward Na+ gradient failed to stimulate [3H]PAH uptake compared with K+ or Li+ and did not cause intravesicular PAH accumulation above equilibrium distribution. In the absence of Na+, the dicarboxylates glutarate and suberate cis-inhibited and trans-stimulated [3H]PAH uptake, indicating a common transport system. In the presence of Na+, 10 microM glutarate in the incubation medium did not cis-inhibit, but rather stimulated [3H]PAH uptake and caused PAH accumulation above equilibrium distribution ("overshoot"). Li+ diminished this stimulation, but was without effect on [3H]PAH/PAH- and [3H]PAH/glutarate exchange. The data indicate the coexistence of a Na+ -coupled, Li+-sensitive transport system for dicarboxylates and a Li+ -insensitive PAH/dicarboxylate exchanger in the basolateral membrane. We propose that dicarboxylates are cotransported with Na+ into the cell and subsequently exchange for extracellular PAH at the basolateral membrane. PAH uptake is thereby indirectly coupled to Na+ via the Na+/dicarboxylate cotransporter.
为了研究对氨基马尿酸（PAH）跨肾小管对侧膜摄取并在近端小管细胞中浓缩的机制，我们用大鼠肾皮质制备的基底外侧膜囊泡进行了实验。与钾离子或锂离子相比，内向钠离子梯度未能刺激[3H]PAH的摄取，也未导致囊泡内PAH在平衡分布之上的积累。在没有钠离子的情况下，二羧酸盐戊二酸和辛二酸顺式抑制并反式刺激[3H]PAH的摄取，表明存在共同的转运系统。在有钠离子存在的情况下，孵育培养基中10微摩尔的戊二酸并不顺式抑制，而是刺激[3H]PAH的摄取，并导致PAH在平衡分布之上的积累（“过冲”）。锂离子减弱了这种刺激，但对[3H]PAH/PAH-和[3H]PAH/戊二酸的交换没有影响。数据表明，在基底外侧膜中存在一种钠离子偶联、对锂离子敏感的二羧酸盐转运系统和一种对锂离子不敏感的PAH/二羧酸盐交换体。我们提出，二羧酸盐与钠离子协同转运进入细胞，随后在基底外侧膜与细胞外PAH进行交换。因此，PAH的摄取通过钠离子/二羧酸盐共转运体间接与钠离子偶联。
