Efflux of dietary flavonoid quercetin 4'-beta-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2.
Although there is strong evidence to suggest that flavonoid consumption is beneficial to human health, the extent to which flavonoids are absorbed and the mechanisms involved are controversial. Contrary to common dogma, we previously demonstrated that quercetin 4'-beta-glucoside, the predominant form of the most abundant dietary flavonoid, quercetin, was not absorbed across Caco-2 cell monolayers. The aim of this study was to test the hypothesis that a specific efflux transporter is responsible for this lack of absorption. Transport of quercetin 4'-beta-glucoside, alone or with inhibitors, was examined with Caco-2 cell monolayers. In addition, subcellular localization of the multidrug resistance-associated proteins MRP1 and MRP2 was examined by immunofluorescent confocal microscopy. Efflux of quercetin 4'-beta-glucoside, a saturable process, was not altered by verapamil, a P-glycoprotein inhibitor, but was competitively inhibited by MK-571, an MRP inhibitor. These data in combination with immunofluorescent localization of MRP2 to the apical membrane support a role for MRP2 in the intestinal transcellular efflux of quercetin 4'-beta-glucoside. These results suggest a role for MRP2 in the transport of a new class of agents, dietary glucosides.
Walgren
R A
RA
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Karnaky
K J
KJ
Lindenmayer
G E
GE
Walle
T
T
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D000042:Absorption; D001692:Biological Transport; D018938:Caco-2 Cells; D018432:Drug Resistance, Multiple; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D026901:Membrane Transport Proteins; D018613:Microscopy, Confocal; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011794:Quercetin; C000715087:ABCC2 protein, human; C080613:spiraeoside; C421109:multidrug resistance-associated protein 1