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 language | English |
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Pages (from-to) | 741-745 |
Number of pages | 5 |
Journal | Biological and Pharmaceutical Bulletin |
Volume | 32 |
Issue number | 4 |
DOIs | |
State | Published - 2009/04 |
Keywords
- Intestinal absorption
- LS180 cell
- Mizoribine
- Nucleoside transporter
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science