The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells

• Published in: Alimentary pharmacology & therapeutics 2003-07, Vol.18 (s1), p.133-138
• Main Authors: Joh, T., Takezono, Y., Oshima, T., Sasaki, M., Seno, K., Yokoyama, Y., Ohara, H., Nomura, T., Alexander, J. S., Itoh, M.
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Ulcer Agents - pharmacology; Biological and medical sciences; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - pharmacokinetics; Drug toxicity and drugs side effects treatment; Epithelial Cells - metabolism; Gastric Mucosa - metabolism; Indomethacin - pharmacology; Medical sciences; Nitrobenzenes - pharmacology; Permeability; Pharmacology. Drug treatments; Quinolones - pharmacology; Rats; Sulfonamides - pharmacology; Toxicity: digestive system
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1046/j.1365-2036.18.s1.15.x

Summary 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. Aim : 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.