title: Rebamipide binds to iNOS-positive cells in acetic acid-treated but not in ethanol-treated rat gastric mucosa.
abstract: BACKGROUND
  Rebamipide is a gastroprotective agent to stimulate prostaglandin generation in gastric mucosa and attenuate the activity of neutrophils, but direct evidence for the effector sites of this agent has remained to be clarified.
  
  
  OBJECTIVE
  The present study was undertaken to show the effector sites of rebamipide in control and ulcer-provoked rats.
  
  
  METHODS
  The rats were divided into control, acetic acid- and ethanol-treated rats. In the acetic acid-treated group, 100% acetic acid was attached to the serosal surface of the stomach for 30 s, 7 days before the experiments. In the ethanol-treated group, a dose of 0.5 mL/100 g body weight of 50% ethanol was administered through orogastric intubation 2 h before the experiments. Using the unfixed cryostat sections, aqueous solution of 3H-rebamipide was applied and the localization of the binding sites of rebamipide was investigated by autoradiography.
  
  
  RESULTS
  In the control rats, rebamipide was found to bind to the surface epithelial cells. In the ethanol-treated group, few binding sites were observed in the damaged gastric mucosa. In the acetic acid-treated group, the marked accumulation of the binding sites of 3H-rebamipide was observed in the mesenchymal cells in the lamina propria mucosae between the regenerated gastric epithelial cells. Combination of autoradiography and immunohistochemistry has revealed that iNOS-immunoreactive cells had the strong binding of rebamipide in the acetic acid-treated group. Some of these cells were CD68-positive macrophages, while others were CD68-negative, corresponding to polymorphonuclear leucocytes. In the ethanol-treated acute gastric mucosal injury group, few binding sites were observed in the damaged gastric mucosa.
  
  
  CONCLUSIONS
  Autoradiography has made it clear that rebamipide binds to iNOS-positive cells in the gastric mucosa 7 days after acetic acid-treatment.
authors.affiliation: Center for Basic Research, the Kitasato Institute, Tokyo, Japan. nakamura-m@kitasato.or.jp
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Akiba
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Tsuchimoto
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001665:Binding Sites; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D007202:Indicators and Reagents / Q000494:pharmacology; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D015363:Quinolones / Q000378:metabolism*; D051381:Rats; D012997:Solvents / Q000494:pharmacology; D013276:Stomach Ulcer / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D007202:Indicators and Reagents; D015363:Quinolones; D012997:Solvents; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C052785:rebamipide; D000409:Alanine; D019342:Acetic Acid