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

Abstract

Background & Aims: This study assessed the expression of the recently identified adenosine triphosphate–dependent bile salt export pump and the functional ability to excrete bile salts in cholestatic models in the rat. Methods: The effects of common bile duct ligation, endotoxin, and ethinylestradiol on bile salt export pump messenger RNA levels, protein expression, and tissue localization were determined. Changes in the expression of 3 other hepatocyte membrane transporters (Na + taurocholate cotransporter, multispecific organic anion transporter, and P-glycoprotein) were also determined for comparison. Functional assessment of bile salt excretion was determined after bile duct ligation. Results: Expression of the bile salt export pump was diminished but relatively preserved compared with other membrane transporters. Tissue localization of the bile salt export pump persisted at the canalicular domain in all 3 models. In contrast, expressions of the Na + taurocholate cotransporter and multispecific organic anion transporter were more profoundly diminished. P-glycoprotein levels increased severalfold with common bile duct ligation but were unchanged with either endotoxin or ethinylestradiol. The capacity to excrete bile salts was relatively maintained 3 and even 14 days after bile duct ligation. Conclusions: Alterations in expression of the bile salt export pump may account for the functional alterations of bile salt secretion observed in cholestasis. However, relative preservation of expression is associated with persistent bile salt excretion and may lessen the extent of liver injury produced by bile salt retention. GASTROENTEROLOGY 2000;118:163-172