Expression of the bile salt export pump is maintained after chronic cholestasis in the rat

Background & Aims: This study assessed the expression of the recently ident ified adenosine triphosphate-dependent bile salt export pump and the functi onal ability to excrete bile salts in cholestatic models in the rat. Method s: The effects of common bile duct ligation, endotoxin, and ethinylestradio l on bile salt export pump messenger RNA levels, protein expression, and ti ssue localization were determined, Changes in the expression of 3 other hep atocyte membrane transporters (Na+ taurocholate cotransporter, multispecifi c organic anion transporter, and P-glycoprotein) were also determined for c omparison. Functional assessment of bile salt excretion was determined afte r bile duct ligation. Results: Expression of the bile salt export pump was diminished but relatively preserved compared with other membrane transporte rs. Tissue localization of the bile salt export pump persisted at the canal icular domain in all 3 models. In contrast, expressions of the Na+ taurocho late cotransporter and multispecific organic anion transporter were more pr ofoundly diminished. P-glycoprotein levels increased severalfold with commo n bile duct ligation but were unchanged with either endotoxin or ethinylest radiol. The capacity to excrete bile salts was relatively maintained 3 and even 14 days after bile duct ligation, Conclusions: Alterations in expressi on of the bile salt export pump may account for the functional alterations of bile salt secretion observed in cholestasis. However, relative preservat ion of expression is associated with persistent bile salt excretion and may lessen the extent of liver injury produced by bile salt retention.