CALCEIN IS EXCRETED FROM THE INTESTINAL MUCOSAL CELL-MEMBRANE BY THE ACTIVE-TRANSPORT SYSTEM

In this study, we report th, efflux mechanism of calcein, an organic a nion, mediated by a multidrug resistance-associated protein (MRP)-like protein in the intestinal mucosal membrane. The transport of calcein from the mucosal to serosal side was decreased dose-dependently and wa s significantly lower than that of the opposite direction. In addition , its transport was increased in the presence of metabolic inhibitors and probenecid. Furthermore, the efflux of calcein from the intestinal cell membrane, which was preloaded with calcein acetoxymethyl ester, was predominantly observed in the mucosal side rather than in the sero sal side. Its efflux to the mucosal side was inhibited by the metaboli c inhibitors and probenecid, not by verapamil which is a p-glycoprotei n substrate. These results indicated that the transport of calcein and possibly other organic anions across the intestinal membrane may be r egulated by the MRP-like protein, but not P-glycoprotein.