title: Protective effect of excitatory amino acids on cold-restraint stress-induced gastric ulcers in mice: role of cyclic nucleotides.
abstract: Previous studies have shown that excitatory amino acids (EAAs) and their receptors may play important roles in the mammalian enteric system. In this study, we investigated whether EEAs, including L-glutamate (L-Glu) and subtypes N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA), reduce cyclic AMP (cAMP) levels and play a role in protecting gastric lesions in cold-restraint stress (CRS) mice. First, we found that dose-dependent administration of four selected EAAs significantly attenuated the increase 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, pretreatment with 0.25 microg/kg or 0.5 microg/kg dibutyryl cGMP (db-cGMP) exhibited protective effects on CRS-induced gastric lesions, with preventive ratios of 24.61% and 35.32%, respectively. Moreover, db-cGMP at 0.5 microgg/kg significantly attenuated the increase in both cAMP content and the cAMP/cGMP ratio in CRS-treated gastric mucosa. In contrast, db-cAMP exhibited no protective effect, and significantly decreased cGMP content and increased the cAMP/cGMP ratio. These results suggest that EAAs significantly reduce CRS-induced gastric ulcers in mice. The possible mechanism of the antiulcer activity of EAAs 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 involved in CRS-induced gastric ulcer formation in mice.
authors.affiliation: Department of Internal Medicine College of Medicine, Taipei Medical University, Taiwan.
authors.forename: S H
authors.initials: SH
authors.lastname: Chen
authors.forename: H L
authors.initials: HL
authors.lastname: Lei
authors.forename: L R
authors.initials: LR
authors.lastname: Huang
authors.forename: L H
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D018846:Excitatory Amino Acids / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013276:Stomach Ulcer / Q000503:physiopathology* / Q000517:prevention & control; D013312:Stress, Physiological / Q000503:physiopathology; D013696:Temperature
chemical_list: D018846:Excitatory Amino Acids; D000242:Cyclic AMP; D006152:Cyclic GMP