Effects of prolonged treatment with compound 48/80 on the gastric mucosa and mast cells in the rat.

Effects of prolonged administration of compound 48/80 (48/80) on the gastric mucosa, serotonin and histamine levels in serum, and mast cells of rats were studied. Daily administration of 48/80 (0.75 mg/kg, i.p.) for 2 or 4 days produced widespread gastric lesions. Further administration of the agent for up to 12 days did not aggravate the lesions which had developed in the early period of administration of the drug. There were only a few visible lesions and numerous healed ones. Almost the same phenomenon was observed with the daily administration of serotonin plus histamine (10 mg/kg each, i.p.) for 2 to 12 days. While 48/80 given for 2 or 4 days increased serotonin and histamine levels in serum, it induced no appreciable increase of these amines after 8 or 12 days of treatment. Serotonin and histamine levels in peritoneal mast cells significantly decreased after the treatment with 48/80 over a 4 day period. The decrease in gastric lesions after prolonged treatment with 48/80 is due to both the depletion of serotonin and histamine from mast cells and an increased resistance of the gastric mucosa with healed lesions.