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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen.

The purpose of this study is to examine the significance of efflux transporters in the small intestine to extrude glucuronide (G) and sulfate (S) conjugates into the intestinal lumen. From this standpoint, we performed in situ intestinal perfusion experiments by using Eisai hyperbilirubinemic rats (EHBRs) in which the multidrug resistance protein 2 (Mrp2/Abcc2) is hereditarily defective and breast cancer resistance protein (Bcrp1/ Abcg2) knockout mice. The intestinal lumen of EHBRs and Bcrp1 (-/-) mice was perfused with medium containing 4-methylumbelliferone (4MU) and E3040 [6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridilmethyl) benzothiazole] to determine the efflux of metabolites into the outflow. The efflux of E3040-glucuronide (G) in EHBRs was significantly lower compared with that in normal rats. However, no significant difference was observed for the efflux of 4MU-G, 4MU-sulfate (S), and E3040-S between EHBRs and normal rats. In contrast, the efflux of intracellularly formed 4MU-G, 4MU-S, and E3040-G in Bcrp1 (-/-) mice was significantly lower than that in normal mice. Therefore, Bcrp1 has an important role in extruding glucuronide and sulfate conjugates formed in enterocytes into the intestinal lumen, whereas Mrp2 is responsible for the efflux of some glucuronide conjugates.[1]


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