Corticosteroids modulate the secretory processes of the rat intrahepatic biliary epithelium

Abstract

Background & Aims: We investigated the expression of glucocorticoid receptors (GcRs) in the intrahepatic bili-ary 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 bi-carbonate excretion and H /HCO 3 transport processes were investigated in bile fistula rats, isolated intrahe-patic bile duct units (IBDUs), and purified cholangio-cytes. Results: GcRs were expressed by rat cholangio-cytes. Although acute administration of corticosteroids showed no effect, treatment for 2 days with dexameth-asone or budesonide increased (P < 0.05) biliary bicar-bonate 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 /HCO 3 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.