RGD Reference Report - Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. - Rat Genome Database

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Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2.

Authors: Hosomi, A  Nakanishi, T  Fujita, T  Tamai, I 
Citation: Hosomi A, etal., PLoS One. 2012;7(2):e30456. doi: 10.1371/journal.pone.0030456. Epub 2012 Feb 10.
RGD ID: 11099980
Pubmed: PMID:22348008   (View Abstract at PubMed)
PMCID: PMC3277506   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0030456   (Journal Full-text)

Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
urate transport  IMP 11099980 RGD 

Objects Annotated

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


Additional Information