Calcein is excreted from the intestinal mucosal cell membrane by the active transport system.
In this study, we report the efflux mechanism of calcein, an organic anion, 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 was 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 serosal side. Its efflux to the mucosal side was inhibited by the metabolic inhibitors and probenecid, not by verapamil which is a P-glycoprotein substrate. These results indicated that the transport of calcein and possibly other organic anions across the intestinal membrane may be regulated by the MRP-like protein, but not P-glycoprotein.
Fujita
T
T
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Yamada
H
H
Fukuzumi
M
M
Nishimaki
A
A
Yamamoto
A
A
Muranishi
S
S
D000818:Animals; D001386:Azides / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007583:Jejunum / Q000378:metabolism; D011339:Probenecid / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012076:Renal Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D019810:Sodium Azide; D012969:Sodium Fluoride / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001386:Azides; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012076:Renal Agents; D012969:Sodium Fluoride; D019810:Sodium Azide; D014700:Verapamil; D011339:Probenecid; C007740:fluorexon; D003630:Daunorubicin