Efflux of intracellular α-ketoglutarate via p-aminohippurate /dicarboxylate exchange in OK kidney epithelial cells

The involvement of intracellular α-ketoglutarate (α-KG) in p- aminohippurate (PAH) transport was investigated in OK kidney epithelial cells. Efflux of intracellular α-KG from the OK cells to the basolateral side was increased by applying PAH to the basolateral side of the cells. In contrast, the intracellular α-KG concentration was not influenced by the addition of PAH. The α-KG efflux across the basolateral membrane induced by PAH was higher than that across the apical membrane. Probenecid inhibited the PAH-dependent α-KG efflux. The α-KG efflux to the basolateral side was saturable with increasing concentration of PAH in the basolateral medium. Antimycin A, a metabolic inhibitor, inhibited [¹⁴C]PAH uptake across the basolateral membrane of OK cells in a dose-dependent manner. In addition, both the α-KG efflux induced by PAH and the intracellular α-KG concentration were decreased, by antimycin A dose-dependently. These results directly show that α-KG generated by intracellular metabolism is effluxed via PAH/dicarboxylate exchange in the basolateral membrane of OK cells.