Protective effect of excitatory amino acids on cold-restraint stress-induced gastric ulcers in mice - Role of cyclic nucleotides

Previous studies have shown that excitatory amino acids (EAAs) and their re ceptors may play important roles in the mammalian enteric system. In this s tudy, we investigated whether EEAs, including L-glutamate (L-Glu) and subty pes N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA) , reduce cyclic AMP (cAMP) levels and play a role in protecting gastric les ions in cold-restraint stress (CRS) mice. First, we found that dose-depende nt administration of four selected EAAs significantly attenuated the increa se of cAMP content and exhibited a protective effect on the development of gastric lesions induced by CRS. Second, CRS treatment exhibited a decrease of cGMP content and an increase of cAMP content with marked time-dependent changes, and a high cAMP/cGMP ratio in mice gastric mucosa. Third, pretreat ment with 0.25 mug/kg or 0.5 mug/kg dibutyryl cGMP (db-cGMP) exhibited prot ective effects on CRS-induced gastric lesions, with preventive ratios of 24 .61% and 35.32%, respectively. Moreover, db-cGMP at 0.5 mug/kg significantl y attenuated the increase in both cAMP content and the cAMP/cGMP ratio in C RS-treated gastric mucosa. In contrast, db-cAMP exhibited no protective eff ect, and significantly decreased cGMP content and increased the cAMP/cGMP r atio. These results suggest that EAAs significantly reduce CRS-induced gast ric ulcers in mice. The possible mechanism of the antiulcer activity of EAA s may be related to a decrease in the cAMP content in the gastric mucosa of mice. In addition, an increase of the cAMP/cGMP ratio significantly involv ed in CRS-induced gastric ulcer formation in mice.