Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1

Tomoko Sato, Satohiro Masuda, Atsushi Yonezawa, Yuko Tanihara, Toshiya Katsura, Ken ichi Inui

研究成果: ジャーナルへの寄稿学術誌査読

72 被引用数 (Scopus)

抄録

To clarify the transcellular transport of organic cations via basolateral and apical transporters, we established double-transfected Madin-Darby canine kidney (MDCK) cells expressing both human organic cation transporter hOCT1 and hMATE1 (MDCK-hOCT1/hMATE1), and hOCT2 and hMATE1 (MDCK-hOCT2/hMATE1) as models of human hepatocytes and renal epithelial cells, respectively. Using the specific antibodies, hOCT1 and hMATE1 or hOCT2 and hMATE1 were found to be localized in the basolateral and apical membranes of MDCK-hOCT1/hMATE1 or MDCK-hOCT2/hMATE1 cells, respectively. A representative substrate, [14C]tetraethylammonium, was transported unidirectionally from the basolateral to apical side in these double transfectants. The optimal pH was showed to be 6.5 for the transcellular transport of [14C]tetraethylammonium, when the pH of the incubation medium on the apical side was varied from 5.5 to 8.5. The basolateral-to-apical transport also decreased in the presence of 10 mM 1-methyl-4-phenylpyridinium or 1 mM levofloxacin on the basolateral side of both double transfectants. In MDCK-hOCT2/hMATE1 cell monolayers, but not in MDCK-hOCT1/hMATE1 cell monolayers, the accumulation of [14C]tetraethylammonium was decreased in the presence of 10 mM 1-methyl-4-phenylpyridinium, but significantly increased in the presence of 1 mM levofloxacin. The uptake of [14C]tetraethylammonium, [3H]1-methyl-4-phenylpyridinium, [14C]metformin and [3H]cimetidine, but not of [14C]procainamide and [3H]quinidine, by HEK293 cells was stimulated by expression of the hOCT1, hOCT2 or hMATE1 compared to control cells. However, transcellular transport of [14C]procainamide and [3H]quinidine was clearly observed in both double-transfectants. These cells could be useful for examining the routes by which compounds are eliminated, or predicting transporter-mediated drug interaction.

本文言語英語
ページ(範囲)894-903
ページ数10
ジャーナルBiochemical Pharmacology
76
7
DOI
出版ステータス出版済み - 10月 1 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 薬理学

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「Transcellular transport of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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