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Presence of an H+/Quinidine Antiport System in Madin–Darby Canine Kidney Cells

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Abstract

Background and Objectives

We have recently found an H+/quinidine antiport system in human kidney HEK 293 cells. The aim of the present study was to evaluate whether the H+/quinidine antiport system is expressed in Madin–Darby canine kidney (MDCK) cells.

Methods

We investigated the uptake and efflux of quinidine in MDCK cells.

Results

The uptake of 100 µM quinidine into MDCK cells was decreased by acidification of extracellular pH or alkalization of intracellular pH. In addition, the uptake of quinidine was highly temperature sensitive, but was extracellular Na+ and membrane potential independent. Furthermore, tetraethylammonium, a typical substrate of renal organic cation transporters, did not inhibit the uptake of quinidine in MDCK cells. On the other hand, lipophilic cationic drugs, such as clonidine, bisoprolol, diphenhydramine, pyrilamine, and imipramine, significantly decreased the uptake of quinidine in MDCK cells. The uptake of quinidine was saturable, and the Michaelis–Menten constant was estimated to be approximately 0.5 mM. In addition, the efflux of quinidine from MDCK cells was increased by the acidification of extracellular pH, suggesting that the transport system mediates not only the uptake, but also secretion of quinidine.

Conclusions

The present findings suggested that the renal new antiport system is involved in the bidirectional membrane transport of quinidine in MDCK cells.

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Authors and Affiliations

  1. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Miki Fukao, Eri Kondo, Hiroki Nishino, Ryutaro Hattori, Asuka Horie & Yukiya Hashimoto

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  1. Miki Fukao
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  2. Eri Kondo
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  3. Hiroki Nishino
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  4. Ryutaro Hattori
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  5. Asuka Horie
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  6. Yukiya Hashimoto
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Corresponding author

Correspondence to Yukiya Hashimoto.

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Funding

This work was supported by JSPS KAKENHI Grant Number 15K08069.

Conflict of interest

MF, EK, HN, RH, AH and YH declare no conflicts of interest.

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Fukao, M., Kondo, E., Nishino, H. et al. Presence of an H+/Quinidine Antiport System in Madin–Darby Canine Kidney Cells. Eur J Drug Metab Pharmacokinet 41, 819–824 (2016). https://doi.org/10.1007/s13318-015-0314-1

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  • DOI: https://doi.org/10.1007/s13318-015-0314-1

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