Cargando…
Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2
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...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277506/ https://www.ncbi.nlm.nih.gov/pubmed/22348008 http://dx.doi.org/10.1371/journal.pone.0030456 |
_version_ | 1782223503196422144 |
---|---|
author | Hosomi, Atsushi Nakanishi, Takeo Fujita, Takuya Tamai, Ikumi |
author_facet | Hosomi, Atsushi Nakanishi, Takeo Fujita, Takuya Tamai, Ikumi |
author_sort | Hosomi, Atsushi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3277506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32775062012-02-17 Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 Hosomi, Atsushi Nakanishi, Takeo Fujita, Takuya Tamai, Ikumi PLoS One Research Article 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. Public Library of Science 2012-02-10 /pmc/articles/PMC3277506/ /pubmed/22348008 http://dx.doi.org/10.1371/journal.pone.0030456 Text en Hosomi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hosomi, Atsushi Nakanishi, Takeo Fujita, Takuya Tamai, Ikumi Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title | Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title_full | Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title_fullStr | Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title_full_unstemmed | Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title_short | Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2 |
title_sort | extra-renal elimination of uric acid via intestinal efflux transporter bcrp/abcg2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277506/ https://www.ncbi.nlm.nih.gov/pubmed/22348008 http://dx.doi.org/10.1371/journal.pone.0030456 |
work_keys_str_mv | AT hosomiatsushi extrarenaleliminationofuricacidviaintestinaleffluxtransporterbcrpabcg2 AT nakanishitakeo extrarenaleliminationofuricacidviaintestinaleffluxtransporterbcrpabcg2 AT fujitatakuya extrarenaleliminationofuricacidviaintestinaleffluxtransporterbcrpabcg2 AT tamaiikumi extrarenaleliminationofuricacidviaintestinaleffluxtransporterbcrpabcg2 |