title: Mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells.
abstract: The aim of the present study was to investigate the mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells. The mRNA of not only organic cation transporter (OCT) 3, but also OCT1 and OCT2, was expressed in Caco-2 cells. The uptake of 100 µm metformin at the apical membrane of Caco-2 cells grown on porous filter membrane was significantly greater than that at the basolateral membrane. The apical uptake of 100 µm metformin in Caco-2 cells grown on plastic dishes was inhibited significantly by 1 mm unlabeled metformin, quinidine and pyrilamine, indicating that a specific transport system is involved in the apical uptake of metformin in Caco-2 cells. The apical uptake of 100 µm metformin in Caco-2 cells was decreased by acidification of the medium, but not increased by alkalization. In addition, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (a protonophore) had no effect on the apical uptake of metformin in Caco-2 cells at apical medium pH 8.4. These findings suggested that the apical uptake of metformin in Caco-2 cells is mediated at least partly by OCTs, but that the postulated H(+) /tertiary amine antiport system is not responsible for the apical uptake of metformin.
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.forename: Jumpei
authors.initials: J
authors.lastname: Sakata
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
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: D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008687:Metformin / Q000493:pharmacokinetics*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D000099254:Organic Cation Transporter 3
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D000099254:Organic Cation Transporter 3; C491013:SLC22A2 protein, human