title: Membrane transport mechanisms of quinidine and procainamide in renal LLC-PK1 and intestinal LS180 cells.
abstract: The aim of the present study was to compare the membrane transport mechanisms of procainamide with those of quinidine using renal epithelial LLC-PK(1) and intestinal epithelial LS180 cells. In LLC-PK(1) cells, the transcellular transport of 10 microM quinidine in the basolateral-to-apical direction was similar to that in the opposite direction, and 1 mM tetraethylammonium (TEA) did not affect the transcellular transport of the drug. On the other hand, the transcellular transport of 10 microM TEA and procainamide in LLC-PK(1) cells was directional from the basolateral side to the apical side. In addition, this directional transcellular transport of procainamide was diminished in the presence of 1 mM TEA. In LS180 cells, the temperature-dependent cellular uptake of 100 microM quinidine and procainamide was markedly increased by alkalization of the apical medium, and was inhibited significantly by 1 mM several hydrophobic cationic drugs, but not by TEA. The rank order of the inhibitory effects of hydrophobic cationic drugs on the uptake of procainamide in LS180 cells was imipramine>quinidine>diphenhydramine asymptotically equal topyrilamine>procainamide, which was consistent with that on the uptake of quinidine. These findings suggested that procainamide (but not quinidine) was transported by cation transport systems in renal epithelial cells, but that both procainamide and quinidine were taken up by another cation transport system in intestinal epithelial cells.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Masago
authors.forename: Mari
authors.initials: M
authors.lastname: Takaai
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sakata
authors.forename: Asuka
authors.initials: A
authors.lastname: Horie
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ito
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishida
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004347:Drug Interactions; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D018374:LLC-PK1 Cells; D011342:Procainamide / Q000493:pharmacokinetics*; D011802:Quinidine / Q000493:pharmacokinetics*; D013552:Swine; D013696:Temperature; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D019789:Tetraethylammonium; D011802:Quinidine; D011342:Procainamide