RRC ID 41944
著者 Joh T, Takezono Y, Oshima T, Sasaki M, Seno K, Yokoyama Y, Ohara H, Nomura T, Alexander JS, Itoh M.
タイトル The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells.
ジャーナル 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.
巻・号 18 Suppl 1
ページ 133-8
公開日 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
引用数 12
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)