RGD Reference Report - Role of breast cancer resistance protein (Bcrp1/Abcg2) in the extrusion of glucuronide and sulfate conjugates from enterocytes to intestinal lumen. - Rat Genome Database

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

Authors: Adachi, Y  Suzuki, H  Schinkel, AH  Sugiyama, Y 
Citation: Adachi Y, etal., Mol Pharmacol. 2005 Mar;67(3):923-8. Epub 2004 Dec 14.
RGD ID: 11099974
Pubmed: PMID:15598971   (View Abstract at PubMed)
DOI: DOI:10.1124/mol.104.007393   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glucuronoside metabolic process  IMP 11099974 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcg2  (ATP binding cassette subfamily G member 2)


Additional Information