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The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells
Author(s) -
Joh T.,
Takezono Y.,
Oshima T.,
Sasaki M.,
Seno K.,
Yokoyama Y.,
Ohara H.,
Nomura T.,
Alexander J. S.,
Itoh M.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.18.s1.15.x
Subject(s) - indometacin , rebamipide , prostaglandin e2 , barrier function , cyclooxygenase , pharmacology , medicine , prostaglandin , paracellular transport , permeability (electromagnetism) , tight junction , prostaglandin e , mannitol , chemistry , biochemistry , biology , microbiology and biotechnology , enzyme , prostaglandin endoperoxide synthase , membrane
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 14 C‐mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E 2 (PGE 2 ) production in culture medium was also measured. Results : Indometacin gradually and significantly decreased TER and increased 14 C‐manitol permeability. Rebamipide reversed the indometacin‐induced changes in epithelial permeability and induced PGE 2 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 PGE 2 . COX‐1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin‐induced increase in gastric epithelial permeability by increasing PGE 2 levels in a COX‐2 dependent manner.