Abstract
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.
Footnotes
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Send reprint requests to: Professor Ken-ichi Inui, Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-01, Japan.
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↵1 This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan and by Grants-in-Aid from the Japan Health Sciences Foundation.
- Abbreviations:
- PAH
- p-aminohippurate
- α-KG
- α-ketoglutarate
- PBS
- Dulbecco’s phosphate-buffered saline
- Received August 19, 1997.
- Accepted December 15, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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