Gastro-protective agent rebamipide induces cyclooxygenease-2 (COX-2) in gastric epithelial cells.
Cyclooxyngease-2 (COX-2) is a key enzyme in prostaglandin (PG) synthesis, and COX-2 induction plays an important role in the healing of gastric ulceration. Rebamipide is a gastro-protective agent and attenuates the activity of neutrophils. A number of reports have shown that rebamipide treatment increases PG production in the gastric mucosa {in vivo}. Although its clinical significance in ulcer healing has been demonstrated, {in vitro} evidence remains to be accumulated. Non-transformed rat gastric mucosal cells (RGM1 cells) were stimulated with rebamipide. RT-PCR and Western blot analysis revealed time and dose-dependent transcriptional and translational stimulation of COX-2. PGE(2) was also produced dose-dependently. However, marked COX-2 induction by rebamipide was transient and lasted less than 24 hr. COX-1 expression was unaltered by rebamipide. Reporter assay results confirmed the stimulation of Cox-2 promoter activity by rebamipide. In conclusion, this study provides {in vitro} evidence that rebamipide transcriptionally induces COX-2 and supports the rationale for its clinical use.
Murata
Hiroaki
H
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Yabe
Yuki
Y
Tsuji
Shingo
S
Tsujii
Masahiko
M
Fu
Hai Ying
HY
Asahi
Kayoko
K
Eguchi
Hiroshi
H
Kawano
Sunao
S
Hayashi
Norio
N
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000502:physiology*; D015363:Quinolones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014945:Wound Healing
D000897:Anti-Ulcer Agents; D015363:Quinolones; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C052785:rebamipide; D000409:Alanine