Vol. 285, Issue 2, 422-427, May 1998

Efflux of Intracellular -Ketoglutarate Via p-Aminohippurate/Dicarboxylate Exchange in OK Kidney Epithelial Cells¹

Junya Nagai, Ikuko Yano, Yukiya Hashimoto, Mikihisa Takano and Ken-Ichi Inui

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan

The involvement of intracellular -ketoglutarate (-KG) in p-aminohippurate (PAH) transport was investigated in OK kidney epithelial cells. Efflux of intracellular -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 -KG concentration was not influenced by the addition of PAH. The -KG efflux across the basolateral membrane induced by PAH was higher than that across the apical membrane. Probenecid inhibited the PAH-dependent -KG efflux. The -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 -KG efflux induced by PAH and the intracellular -KG concentration were decreased by antimycin A dose-dependently. These results directly show that -KG generated by intracellular metabolism is effluxed via PAH/dicarboxylate exchange in the basolateral membrane of OK cells.