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Abstract

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.