Membrane transport mechanisms of mizoribine in the rat intestine and human epithelial LS180 cells

Kazuya Ishida, Mari Takaai, Ayano Yotsutani, Masato Taguchi, Yukiya Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 μg at the concentration of 100 μg/ml=386 μm) of mizoribine was absorbed in 40min. In the LS180 cells, ribavirin and inosine reduced the uptake of 400 μm 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 μm 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.

Original languageEnglish
Pages (from-to)741-745
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number4
DOIs
StatePublished - 2009/04

Keywords

  • Intestinal absorption
  • LS180 cell
  • Mizoribine
  • Nucleoside transporter

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Membrane transport mechanisms of mizoribine in the rat intestine and human epithelial LS180 cells'. Together they form a unique fingerprint.

Cite this