Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2
スポンサーリンク
概要
- 論文の詳細を見る
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. © 2012 Hosomi et al.
論文 | ランダム
- PS-123-7 当科における超高齢者大腸癌症例に対する腹腔鏡下手術の短期成績に関する検討(PS-123 ポスターセッション(123)大腸:手術-1,第111回日本外科学会定期学術集会)
- PS-108-8 NK4のHGFを介した癌 : 間質相互作用阻害によるVEGF発現抑制効果(PS-108 ポスターセッション(108)基礎-2,第111回日本外科学会定期学術集会)
- PS-097-6 当院における局所進行直腸癌に対する術前化学放射線療法(PS-097 ポスターセッション(97)大腸:化学療法-4,第111回日本外科学会定期学術集会)
- PS-089-2 サブグループ解析による腹水洗浄細胞診陽性胃癌の治療戦略(PS-089 ポスターセッション(89)胃:化学療法-1,第111回日本外科学会定期学術集会)
- PS-087-6 IL-6発現が食道癌細胞株の浸潤能に及ぼす影響(PS-087 ポスターセッション(87)食道:基礎-4,第111回日本外科学会定期学術集会)