Bile duct epithelia regulate biliary bicarbonate excretion in normal rat liver.

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 Ca(2+) in cholangiocytes. Livers also were perfused with glucagon or vasopressin to instead increase cAMP or cytosolic Ca(2+) 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.