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The synthetic opioid met-enkephalin analog [D-Ala², MePhe⁴, Met(0)⁵ol] enkephalin (DAMME) and the opiate morphine injected intraperitoneally to rats at doses of 0.5–2 and 5–20 mg/kg, respectively, showed a protective effect on gastric damage induced by oral administration of necrotizing agents (0.6 NHCl or 0.2 NNaOH solutions, 1 ml/rat). The protection was prevented by naltrexone (10 mg/kg s.c), an opioid antagonist with long-lasting activity. Histological sections of mucosal samples from animals pretreated with morphine (10 mg/kg i.p.) and DAMME (1 mg/kg i.p.) showed less alteration of the columnar epithelium, with a normal glandular structure, than untreated rats. A mediation of prostaglandins is suggested, since indomethacin (10 mg/kg s.c.) significantly reduced the protective effects of opioids.