To investigate the possible role of
pepsin in ulceration induced by
hydrogen ion back-diffusion, the ratio of
alkali-labile
pepsinogen to total
pepsinogen was studied during the course of
aspirin- and
taurocholate-induced gastric ulceration in comparison with the changes in the ion permeability and histological findings. The results obtained were as follows. (1) The increase in the
ulcer index was observed between 1 and 2 hr with intragastric
aspirin and between 2 and 4 hr with intragastric
taurocholate. (2) The back-diffusion of
luminal hydrogen ions, observed as a significant decrease in
hydrogen ion net flux, occurred immediately in both cases with
aspirin and with
taurocholate. (3) A significant increase in the ratio of
alkali-labile to total
pepsinogen in the homogenate of gastric mucosa was observed at 30 min with
aspirin and at 60 min with
taurocholate. (4) Histological examination revealed the degeneration of mucosal cells spreading from the
luminal surface into the mucosa, which fell off after 120 min with
aspirin. These findings indicate that the activated
pepsin is involved in the
ulcer formation caused by the
hydrogen ion back-diffusion, although the origin of the activated
pepsin is not clear at the present time.