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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. 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Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2
https://doi.org/10.24517/00014984
https://doi.org/10.24517/00014984618794c1-549b-41c2-80af-9b372c1b4794
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-04 | |||||
タイトル | ||||||
タイトル | Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2 | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
ID登録 | ||||||
ID登録 | 10.24517/00014984 | |||||
ID登録タイプ | JaLC | |||||
著者 |
Hosomi, Atsushi
× Hosomi, Atsushi× Nakanishi, Takeo× Fujita, Takuya× Tamai, Ikumi |
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著者別表示 |
中西, 猛夫
× 中西, 猛夫× 玉井, 郁巳 |
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書誌情報 |
PLoS ONE 巻 7, 号 2, p. e30456, 発行日 2012-01-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1932-6203 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0030456 | |||||
出版者 | ||||||
出版者 | Public Library of Science | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Urinary excretion accounts for two-thirds of total elimination of uri |