The relationships between indomethacine-induced gastric ulcer, ulcer protection by cimetidine and prostacyclin and the cAMP system of the gastric fundic mucosa in the rat.

Gastric ulcer was provoked by indomethacine (20 mg/kg s.c.) in rats. The ulcer protection by prostacyclin and cimetidine as well as the changes of tissue cAMP level in the gastric fundic mucosa--during ulcer-provocation and ulcer protection--were studied. The animals received prostacyclin (125, 250 and 500 micrograms/kg) and cimetidine (2.5 and 50 mg/kg) together with indomethacine. Evaluation of the results was undertaken 4 hours after the administration of the provoking agent. The number and severity of the ulcers as well as the cAMP level of the gastric fundic mucosa were measured. The following results were obtained: (1) cAMP level of the gastric fundic mucosa remained unaltered at the time of ulcer provocation; (2) cimetidine and prostacyclin reduced the number and severity of the ulcers in a dose-dependent manner; (3) cAMP level of the gastric fundic mucosa was reduced after cimetidine and prostacyclin treatment in a dose-dependent manner, the extent of which however did not show any correlation with the degree of ulcer-preventive action. The experimental results indicate that (1) the development of indomethacine-induced gastric ulcer is independent of the ATP--adenylate cyclase--cAMP system of the gastric fundic mucosa; (2) the ulcer protective action of cimetidine and prostacyclin is independent of tissue cAMP system of the gastric fundic mucosa in this model.