Bile duct epithelia regulate biliary bicarbonate excretion in normal rat liver
Bile duct epithelia regulate biliary bicarbonate excretion in normal rat liver
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DOI：
10.1053/gast.2001.26280
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发表时间：
2001-08-01
期刊：
影响因子：
29.4
通讯作者：
Nathanson, MH
中科院分区：
文献类型：
--
作者：
Hirata, K;Nathanson, MH
背景与目的：在胆管细胞中已经发现了许多转运蛋白和通道，但在体内胆管在胆汁形成中所起的作用尚不清楚。我们测定了正常大鼠肝脏胆管细胞对胆汁流动和胆道碳酸氢盐排泄的贡献。方法：由于肝动脉为胆管提供血液供应，分别经门静脉和肝动脉灌注的离体大鼠肝脏，测量胆汁流量和胆道碳酸氢盐。肝脏灌注分泌素或乙酰胆碱（ACh），分别增加胆管细胞中腺苷3′，5′-环单磷酸腺苷（cAMP）或胞浆Ca2+。肝脏也灌注胰高血糖素或加压素，以增加肝细胞的cAMP或胞浆Ca2+。结果：分泌素以剂量依赖的方式增加胆汁碳酸氢盐，通过肝动脉给药更有效。分泌素不影响胆汁流动。同样，乙酰胆碱通过肝动脉而不是门静脉注入时，会增加碳酸氢盐的排泄。乙酰胆碱能增强促分泌素的作用，而环孢素a能抑制促分泌素的作用。乙酰胆碱的作用可被4,4′-二异硫氰酸-2,2′-二磺酸（DIDS）、5-硝基-（3-苯丙胺）苯甲酸（NPPB）或二苯胺-2-羧酸（DPC）阻断，促分泌素的作用可被NPPB或DPC抑制，不受DIDS的影响。胰高血糖素和利尿加压素均未改变胆汁碳酸氢盐。结论：正常大鼠肝脏中胆道碳酸氢盐受胆管细胞而非肝细胞调节。乙酰胆碱诱导的碳酸氢盐排泄依赖于氯离子通道和碳酸氢盐交换，而分泌素诱导的碳酸氢盐排泄独立于碳酸氢盐交换。
Background & Aims: A number of transporters and channels have been identified in cholangiocytes, but the role that bile ducts play in the formation of bile in vivo is unclear. We determined the contribution of cholangiocytes to bile flow and biliary bicarbonate excretion in normal rat liver. Methods: Bile flow and biliary bicarbonate were measured in isolated rat livers perfused via both the portal vein and the hepatic artery because the hepatic artery provides the blood supply to bile ducts. Livers were perfused with secretin or acetylcholine (ACh), which respectively increase either adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+ in cholangiocytes. Livers also were perfused with glucagon or vasopressin to instead increase cAMP or cytosolic Ca2+ in hepatocytes. Results: Secretin increased biliary bicarbonate in a dose-dependent fashion and was much more effective when administered via the hepatic artery. Secretin did not affect bile flow. Similarly, ACh increased bicarbonate excretion when infused via the hepatic artery but not the portal vein. The effects of secretin were augmented by ACh, and this was prevented by cyclosporin A. The effects of ACh were blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), 5-nitro2-(3-phenylpropylamino)benzoic acid (NPPB), or diphenylamine-2-carboxylic acid (DPC), and the effects of secretin were inhibited by NPPB or DPC and unaffected by DIDS. Neither glucagon nor vasopressin altered biliary bicarbonate. Conclusions: Biliary bicarbonate is regulated by cholangiocytes rather than hepatocytes in normal rat liver. ACh-induced bicarbonate excretion depends on both chloride channels and bicarbonate exchange, whereas secretin-induced bicarbonate excretion is independent of bicarbonate exchange.