title: The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells.
abstract: BACKGROUND
  Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin.
  
  
  OBJECTIVE
  Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability.
  
  
  METHODS
  Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10-7 M). Trans-epithelial permeability was measured by TER and diffusion rate of 14C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E2 (PGE2) production in culture medium was also measured.
  
  
  RESULTS
  Indometacin gradually and significantly decreased TER and increased 14C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor.
  
  
  CONCLUSIONS
  COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE2. COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE2 levels in a COX-2 dependent manner.
authors.affiliation: Department of Internal Medicine & Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. tjoh@med.nagoya-cu.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: Y
authors.initials: Y
authors.lastname: Takezono
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Seno
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: J S
authors.initials: JS
authors.lastname: Alexander
authors.forename: M
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000493:pharmacokinetics; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010539:Permeability; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D015363:Quinolones; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine; D007213:Indomethacin