Premium
Rebamipide binds to iNOS‐positive cells in acetic acid‐treated but not in ethanol‐treated rat gastric mucosa
Author(s) -
Nakamura M.,
Akiba Y.,
Matsui H.,
Tsuchimoto K.,
Ishii H.
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.s1.8.x
Subject(s) - rebamipide , acetic acid , lamina propria , gastric mucosa , ethanol , chemistry , stomach , biochemistry , medicine , pharmacology , epithelium , pathology
Summary 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. Aim : 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 3 H‐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 3 H‐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.