Miki Fukao1, Eri Kondo1, Hiroki Nishino1, Ryutaro Hattori1, Asuka Horie1, Yukiya Hashimoto2. 1. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. 2. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. yukiya@pha.u-toyama.ac.jp.
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.
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.
Authors: S Freudenthaler; I Meineke; K H Schreeb; E Boakye; U Gundert-Remy; C H Gleiter Journal: Br J Clin Pharmacol Date: 1998-12 Impact factor: 4.335