Bile acids are synthesized in hepatocytes from cholesterol, conjugated to either taurine or glycine, secreted into bile and, via the bile ducts, reach the small intestine to facilitate lipid absorption (Hofmann, 1994). Subsequently, bile acids are reclaimed at the terminal ileum, returned to the liver via the portal circulation and resecreted into bile, accomplishing their enterohepatic circulation (Hofmann, 1994). At the cellular level, this recycling of bile acids, important for conservation of the bile acid pool, is achieved by the co-ordinated activities of a series of apical and basolateral membrane bile acid transporters expressed on the epithelial cells of the terminal ileum and liver (Dawson & Oelkers, 1995).

The active recovery of conjugated bile acids, the major form of bile acids in bile, in the terminal ileum, is mediated by a Na⁺-driven, bile acid transporter, ASBT, located at the luminal domain of the ileocyte (Dawson & Oelkers, 1995). Following uptake into the ileocyte, bile acids bind to the intestinal bile acid binding protein (I-BABP) in the cytoplasm to be directed across the cell to the basolateral membrane where they enter into the portal venous circulation by a Na⁺-independent mechanism (Dawson & Oelkers, 1995). Subsequently, the majority of conjugated bile acids are efficiently reabsorbed from portal vein blood into hepatocytes, mainly via the sodium taurocholate cotransporter (ntcp) (St-Pierre et al. 2001) and then are secreted into the biliary system primarily via ATP-dependent export pumps located on the apical (i.e. canalicular) domain of hepatocytes (St-Pierre et al. 2001).

As bile percolates through the intrahepatic bile ducts, it undergoes numerous modifications due to both secretory and absorptive activities of the cholangiocytes. We and others have previously shown that biliary epithelia can take up conjugated bile acids via ASBT (Alpini et al. 1997; Lazaridis et al. 1997) expressed on the cholangiocyte apical membrane and identical to the protein cloned from rat ileum and kidney (Shneider et al. 1995; Christie et al. 1996). We have also recently identified an alternatively spliced, truncated transcript of ASBT, designated t-ASBT, that allows cholangiocytes and possibly other bile-acid transporting epithelia (i.e. ileum and kidney) to extrude bile acids at the basolateral domain (Lazaridis et al. 2000). In this presentation, published and unpublished data on bile acid transport in general and in cholangiocytes in particular will be discussed.