title: Temperature-dependent specific transport of levofloxacin in human intestinal epithelial LS180 cells.
abstract: It was reported previously that specific levofloxacin uptake in Caco-2 cells was inhibited by nicotine, enalapril, L-carnitine and fexofenadine. The aim of the present study was to characterize the cellular uptake of levofloxacin using another human intestinal cell line, LS180. Levofloxacin uptake in LS180 cells was temperature-dependent and optimal at neutral pH, but was Na(+)-independent. The rank order of inhibitory effects of the four compounds on [(14)C] levofloxacin uptake in LS180 cells was nicotine>enalapril>L-carnitine>fexofenadine, which is consistent with that in Caco-2 cells. The mRNA levels of OATP1A2, 1B1, 1B3 and 2B1 in LS180 cells were markedly different from those in Caco-2 cells, and OATP substrates/inhibitors had no systematic effect on the levofloxacin uptake. The mRNA levels of OCTN1 and 2 in LS180 cells were similar to those in Caco-2 cells. However, the inhibitory effect of nicotine on L-[(3)H]carnitine uptake was much less potent than that of unlabeled L-carnitine. These results indicate that the specific uptake system for levofloxacin in LS180 cells is identical/similar to that in Caco-2 cells, but that OATPs and OCTNs contribute little to levofloxacin uptake in the human intestinal epithelial cells.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fukumori
authors.forename: Miki
authors.initials: M
authors.lastname: Masago
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishida
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kayano
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects*; D018938:Caco-2 Cells; D002331:Carnitine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D064704:Levofloxacin; D015242:Ofloxacin / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000998:Antiviral Agents; D064704:Levofloxacin; D015242:Ofloxacin; D002331:Carnitine