title: Role of ion transporters in the bile acid-induced esophageal injury.
abstract: 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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; First Department of Medicine, University of Szeged, Szeged, Hungary;
authors.forename: Dorottya
authors.initials: D
authors.lastname: Laczkó
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary;
authors.forename: András
authors.initials: A
authors.lastname: Rosztóczy
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
authors.forename: Klaudia
authors.initials: K
authors.lastname: Birkás
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
authors.forename: Máté
authors.initials: M
authors.lastname: Katona
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary; Department of Pathophysiology, University of Szeged, Szeged, Hungary;
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary;
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary;
authors.forename: Richárd
authors.initials: R
authors.lastname: Róka
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary;
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary; MTA-SZTE Translational Gastroenterology Research Group, University of Szeged, Szeged, Hungary; and Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary; venglovecz.viktoria@med.u-szeged.hu.
authors.forename: Viktória
authors.initials: V
authors.lastname: Venglovecz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D001647:Bile Acids and Salts / Q000378:metabolism / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000071041:Esophageal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007295:Inositol Phosphates / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008679:Metaplasia; D008875:Middle Aged; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013997:Time Factors
chemical_list: D001647:Bile Acids and Salts; D027963:Chloride-Bicarbonate Antiporters; D007295:Inositol Phosphates; D026901:Membrane Transport Proteins; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D002118:Calcium
keywords: bile acids; epithelium; esophagus; ion transporters