title: Corticosteroids modulate the secretory processes of the rat intrahepatic biliary epithelium.
abstract: OBJECTIVE
  We investigated the expression of glucocorticoid receptors (GcRs) in the intrahepatic biliary epithelium and the role of corticosteroids in the regulation of cholangiocyte secretion.
  
  
  METHODS
  GcR was studied by immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blots. The effects of dexamethasone and budesonide on biliary bicarbonate excretion and H+/HCO3- transport processes were investigated in bile fistula rats, isolated intrahepatic bile duct units (IBDUs), and purified cholangiocytes.
  
  
  RESULTS
  GcRs were expressed by rat cholangiocytes. Although acute administration of corticosteroids showed no effect, treatment for 2 days with dexamethasone or budesonide increased (P < 0.05) biliary bicarbonate concentration and secretion, which were blocked by the specific GcR antagonist, RU-486. IBDUs isolated from rats treated with dexamethasone or budesonide showed an increased (P < 0.05) activity of the Na+/H+ exchanger (NHE1 isoform) and Cl-/HCO3- exchanger (AE2 member), which was blocked by RU-486. Protein expression of NHE1 and AE2 and messenger RNA for NH1 but not AE2 were increased (P < 0.05) in isolated cholangiocytes by dexamethasone treatment.
  
  
  CONCLUSIONS
  The intrahepatic biliary epithelium expresses GcR and responds to corticosteroids by increasing bicarbonate excretion in bile. This is caused by corticosteroid-induced enhanced activities and protein expression of transport processes driving bicarbonate excretion in the biliary epithelium.
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University La Sapienza, Rome, Italy. domenico.alvaro@uniroma1.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gigliozzi
authors.forename: Luca
authors.initials: L
authors.lastname: Marucci
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alpini
authors.forename: Barbara
authors.initials: B
authors.lastname: Barbaro
authors.forename: Rita
authors.initials: R
authors.lastname: Monterubbianesi
authors.forename: Lara
authors.initials: L
authors.lastname: Minetola
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mancino
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medina
authors.forename: Adolfo F
authors.initials: AF
authors.lastname: Attili
authors.forename: Antonio
authors.initials: A
authors.lastname: Benedetti
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017920:Antiporters; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000378:metabolism*; D019819:Budesonide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000235:genetics; D064606:SLC4A Proteins; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D000893:Anti-Inflammatory Agents; D017920:Antiporters; D001639:Bicarbonates; D005938:Glucocorticoids; D006727:Hormone Antagonists; D008565:Membrane Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D064606:SLC4A Proteins; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D015735:Mifepristone; D019819:Budesonide; D003907:Dexamethasone