title: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat.
abstract: OBJECTIVE
  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.
authors.affiliation: Liver Center, Yale University School of Medicine, New Haven, Connecticut 06520-8019, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Trauner
authors.forename: C J
authors.initials: CJ
authors.lastname: Soroka
authors.forename: B
authors.initials: B
authors.lastname: Stieger
authors.forename: P J
authors.initials: PJ
authors.lastname: Meier
authors.forename: J L
authors.initials: JL
authors.lastname: Boyer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism*; D002908:Chronic Disease; D018432:Drug Resistance, Multiple; D004997:Ethinyl Estradiol; D008026:Ligation; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D004997:Ethinyl Estradiol; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D012333:RNA, Messenger; D027981:Symporters; C490548:Abcb11 protein, rat; C071908:sodium-bile acid cotransporter