Famotidine prevents deep histologic lesions induced by 0.6N HCl in rat gastric mucosa: role of parietal cells.
The assessment of the protective actions of H2-receptor antagonists against gastric mucosal lesions by necrotizing agents relies on the gross observation of the gastric mucosa only. We examined the activity of famotidine against 0.6 N HCl-induced damage and the role of parietal cells by light and transmission electron microscopy. Rats received famotidine 0.3-10 mg/kg intragastrically. Sixty minutes later 0.6 N HCl (1 ml/rat) was given and after an additional 30 min the stomachs were removed. Macroscopically visible lesions were measured. Histologic lesions were scored on the basis of the depth. The ultrastructure of parietal cells in the isthmus-neck region was examined. Pretreatment with famotidine resulted in a slight increase of macroscopically visible gastric lesions in response to HCl. While the extent of total histologic damage was not modified, the antisecretory dose significantly reduced only lesions deep within the mucosa. Famotidine alone determined the dose-dependent occurrence of a distinct parietal cell morphological state, suggestive of inhibition of the secretory system. A causal link between the protective effect on the region where parietal cells are located, the percentage of cells shifting to the inhibited morphological state, and the inhibitory effect on acid secretion is proposed.
Grandi
D
D
Institute of Anatomy, University of Parma, Italy.
Morini
G
G
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000009:adverse effects*; D008297:Male; D008853:Microscopy; D008854:Microscopy, Electron; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D015738:Famotidine; D006851:Hydrochloric Acid