Reference - Detail
RRC ID | 41944 |
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Author | Joh T, Takezono Y, Oshima T, Sasaki M, Seno K, Yokoyama Y, Ohara H, Nomura T, Alexander JS, Itoh M. |
Title | The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells. |
Journal | Aliment Pharmacol Ther |
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. 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. |
Volume | 18 Suppl 1 |
Pages | 133-8 |
Published | 2003-7-1 |
DOI | 10.1046/j.1365-2036.18.s1.15.x |
PII | 1516 |
PMID | 12925151 |
MeSH | Alanine / analogs & derivatives* Alanine / pharmacology* Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Anti-Ulcer Agents / pharmacology* Cyclooxygenase Inhibitors / pharmacology Dinoprostone / pharmacokinetics Epithelial Cells / metabolism Gastric Mucosa / metabolism* Indomethacin / pharmacology Nitrobenzenes / pharmacology Permeability Quinolones / pharmacology* Rats Sulfonamides / pharmacology |
IF | 7.515 |
Times Cited | 12 |
WOS Category | GASTROENTEROLOGY & HEPATOLOGY PHARMACOLOGY & PHARMACY |
Resource | |
Human and Animal Cells | RGM1(RCB0876) |