title: Membrane transport mechanisms of mizoribine in the rat intestine and human epithelial LS180 cells.
abstract: The aim of the present study was to characterize membrane transport mechanisms of mizoribine in the intestinal epithelial cells. We evaluated the contribution of Na(+)-dependent and -independent membrane transporters to mizoribine absorption in the rat intestine using an in situ closed loop method. In addition, we evaluated the effects of structurally related compounds, extracellular Na(+) concentrations, and an inhibitor of Na(+)-independent equilibrative nucleoside transporter, nitrobenzylmercaptopurine ribonucleoside (NBMPR), on the uptake of mizoribine in human intestinal epithelial LS180 cells. In the presence and also absence of Na(+) in rat intestinal loops, more than 60% of the administered dose (50 microg at the concentration of 100 microg/ml=386 microM) of mizoribine was absorbed in 40 min. In the LS180 cells, ribavirin and inosine reduced the uptake of 400 microM mizoribine with the increasing concentrations (from 5 to 50 mM) of the inhibitors. The cellular uptake of mizoribine in the absence of extracellular Na(+) decreased to 72.7% of the uptake in the presence of extracellular Na(+), whereas 100 microM NBMPR decreased the uptake of mizoribine markedly to 34.7% of that without NBMPR. These findings suggest that Na(+)-independent nucleoside transporters are largely responsible for absorption of mizoribine in the intestine.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishida
authors.forename: Mari
authors.initials: M
authors.lastname: Takaai
authors.forename: Ayano
authors.initials: A
authors.lastname: Yotsutani
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto