title: Presence of an H+/Quinidine Antiport System in Madin-Darby Canine Kidney Cells.
abstract: OBJECTIVE
  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.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fukao
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kondo
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nishino
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Hattori
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Horie
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. yukiya@pha.u-toyama.ac.jp.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D065567:Absorption, Physiological / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D061985:Madin Darby Canine Kidney Cells; D049990:Membrane Transport Modulators / Q000494:pharmacology; D011802:Quinidine / Q000378:metabolism*; D014316:Tritium
chemical_list: D000889:Anti-Arrhythmia Agents; D017920:Antiporters; D049990:Membrane Transport Modulators; D014316:Tritium; D011802:Quinidine; D003000:Clonidine