title: Efflux of intracellular alpha-ketoglutarate via p-aminohippurate/dicarboxylate exchange in OK kidney epithelial cells.
abstract: The involvement of intracellular alpha-ketoglutarate (alpha-KG) in p-aminohippurate (PAH) transport was investigated in OK kidney epithelial cells. Efflux of intracellular alpha-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 alpha-KG concentration was not influenced by the addition of PAH. The alpha-KG efflux across the basolateral membrane induced by PAH was higher than that across the apical membrane. Probenecid inhibited the PAH-dependent alpha-KG efflux. The alpha-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 alpha-KG efflux induced by PAH and the intracellular alpha-KG concentration were decreased by antimycin A dose-dependently. These results directly show that alpha-KG generated by intracellular metabolism is effluxed via PAH/dicarboxylate exchange in the basolateral membrane of OK cells.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nagai
authors.forename: I
authors.initials: I
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Takano
authors.forename: K
authors.initials: K
authors.lastname: Inui
mesh_terms: D000968:Antimycin A / Q000494:pharmacology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
chemical_list: D007656:Ketoglutaric Acids; D000968:Antimycin A; D012964:Sodium; D011339:Probenecid; D010130:p-Aminohippuric Acid