Cytoprotection by histamine in rat gastric mucosa

The effects of histamine on endogenous prostaglandins and on the damage caused by 0.6 N HCl were tested in rat gastric mucosa. The damage was assessed both macroscopically and microscopically. Histamine increased the prostaglandin E2 level in vivo and stimulated the synthesis of prostaglandin E2 and 6-keto-prostaglandin F1 alpha in vitro. These effects of histamine were inhibited by treatment with cimetidine beforehand. Histamine inhibited both the gross visible mucosal damage and deep necrosis caused by the intragastric instillation of 0.6 N HCl. This effect was overcome by cimetidine or indomethacin, but not by diphenhydramine. These results suggest that histamine stimulates prostaglandin synthesis and induces cytoprotection in rat gastric mucosa, perhaps with the involvement of the H2 receptor.