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.