Gastric ulcer formation in cold-stressed mice related to a central calcium-dependent-dopamine synthesizing system

Stress ulceration of the stomach in mice was investigated from the aspect of the calcium/calmodulin-dependent dopamine synthesizing system in the brain. Cold stress was induced in mice by restraining them at 4 degrees C. Serum and brain calcium levels were increased by cold stress, and an increased brain calcium level was found to enhance dopamine synthesis and a successively increased brain dopamine level induced gastric ulcer formation. Development of gastric ulcers elicited by cold stress was significantly decreased by i.p. pretreatment with EDTA (1 micromol/mouse, 1 h before restraint) or alpha-methyltyrosine (a tyrosine hydroxylase inhibitor, 100 mg/kg, 24 h before restraint), and was further significantly increased by pretreatment with CaCl2 (40 micromol/kg, 1 h before restraint). These findings suggest that the development of gastric ulcers in cold-stressed mice may be linked with the enhancement of calcium/calmodulin-dependent catecholamine synthesis in the brain.