Role of ion transporters in the bile acid-induced esophageal injury

Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G16-31. doi: 10.1152/ajpgi.00159.2015. Epub 2016 May 19.


Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury.

Keywords: bile acids; epithelium; esophagus; ion transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / toxicity*
  • Calcium / metabolism
  • Cell Line
  • Chloride-Bicarbonate Antiporters / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Esophageal Mucosa / drug effects*
  • Esophageal Mucosa / metabolism
  • Esophageal Mucosa / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Hydrogen-Ion Concentration
  • Inositol Phosphates / metabolism
  • Ion Transport
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Metaplasia
  • Middle Aged
  • Sodium-Bicarbonate Symporters / metabolism
  • Sodium-Hydrogen Exchangers / metabolism
  • Time Factors


  • Bile Acids and Salts
  • Chloride-Bicarbonate Antiporters
  • Inositol Phosphates
  • Membrane Transport Proteins
  • Sodium-Bicarbonate Symporters
  • Sodium-Hydrogen Exchangers
  • Calcium