Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid.
Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid.
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DOI：
10.4161/chan.22406
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Gründer S
中科院分区：
文献类型：
--
作者：
Wiemuth D;Sahin H;Lefèvre CM;Wasmuth HE;Gründer S
胆汁酸敏感性离子通道（BASIC）是DEG/ENaC基因家族的一员，其功能尚不清楚。大鼠BASIC（rBASIC）在休息时不活动。我们最近已经表明，胆管上皮细胞内衬的胆管，是在肝脏和确定的胆汁酸，特别是猪和鹅去氧胆酸，作为rBASIC的激动剂的BASIC表达的主要网站。此外，似乎细胞外二价阳离子稳定rBASIC的静息状态，因为细胞外二价阳离子的去除打开了通道。在本附录中，我们证明了细胞外二价阳离子的去除增强了胆汁酸对rBASIC的激活，这表明了一种变构机制。此外，我们发现rBASIC被抗胆汁淤积胆汁酸熊去氧胆酸（UDCA）强烈激活，表明BASIC可能介导UDCA的部分治疗作用。
Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA.
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