title: Bile-acid-induced calcium signaling in mouse esophageal epithelial cells.
abstract: In patients with gastroesophageal reflux disease (GERD), esophageal exposure to both acid and duodenogastroesophageal reflux are more common than to acid reflux alone, suggesting that acidic bile acid in duodenal juice may contribute to the pathophysiology and severity of GERD. However, the mechanism whereby esophageal mucosal epithelial cells react to bile acid remains unclear. We visually examined the real-time response of mouse esophageal epithelial cells to bile acids using calcium (Ca(2+))-imaging methods. We investigated the effects of seven different bile acids. After stimulation for a few minutes, only Deoxycholate (DCA) under acidic conditions caused a elevation of intracellular Ca(2+) concentration ([Ca(2+)](i))in the cells in dose- and pH-dependent manners. Conjugated bile acids had no effect on the cells. Viability assay of the cells in the presence of DCA was in good agreement with the calcium imaging data. Besides, DCA-induced [Ca(2+)](i) increase in acidic conditions was observed not only in isolated primary cultured cells, but also in cells in the stratified squamous epithelium. This study suggests that DCA can pass through the anatomical barrier of the esophageal epithelium and induce calcium signaling in epithelial cells in a pH-dependent manner. This supports the hypothesis that bile acid reflux together with gastric acid can affect the esophageal mucosa, even under reflux times of a few minutes.
authors: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan. yamada@anat1.med.osaka-u.ac.jp
authors: Takahiro
authors: T
authors: Yamada
authors: Yusuke
authors: Y
authors: Ishida
authors: Yukiko
authors: Y
authors: Nakamura
authors: Shoichi
authors: S
authors: Shimada
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology / Q000502:physiology*; D020013:Calcium Signaling; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000494:pharmacology / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001647:Bile Acids and Salts; D003840:Deoxycholic Acid