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 H-2-receptor antagonists agains t gastric mucosal Lesions by necrotizing agents relies on the gross observa tion of the gastric mucosa only. We examined the activity of famotidine aga inst 0.6 N HCl-induced damage and the role of parietal cells by light and t ransmission electron microscopy. Rats received famotidine 0.3-10 mg/kg intr agastrically. Sixty minutes later 0.6 N HCl (1 ml/rat) was given and after an additional 30 min the stomachs were removed. Macroscopically visible les ions were measured. Histologic lesions were scored on the basis of the dept h. The ultrastructure of parietal cells in the isthmus-neck region was exam ined. Pretreatment with famotidine resulted in a slight increase of macrosc opically visible gastric lesions in response to HCl. While the extent of to tal histologic damage was not modified, the antisecretory dose significantl y reduced only lesions deep within the mucosa. Famotidine alone determined the dose-dependent occurrence of a distinct parietal cell morphological sta te, 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.