The model of ethanol induced gastric lesions is useful in the evaluation of gastric cytoprotection. We used it to measure cytoprotective effects of two neuropeptides, Met-enkephalin (Peptid-M, LUPEX(R)) and alpha -melanocyte stimulating hormone (alpha -MSH). Both peptides exhibited significant and synergistic cytoprotective effects. The best therapeutic efficacy was obtained with Met-enkephalin and alpha -MSH mixture 3-5:1. Significant cytoprotective action on ethanol induced lesions was also observed by means of two thymus peptide immunomodulators, Thymus Peptide C(R) and JAN 50(R). Thymus Peptide C(R) exhibited a more significant synergistic effect with Met-enkephalin than JAN 50(R). In addition to the cytoprotection of rat gastric mucosa, Met-enkephalin also induced statistically significant and dose dependent Straub tail response versus control in mice. Haloperidol, naloxone and Peptide-D antagonised its effects. NMR spectrospic data supported molecular interaction of Metenkephalin and haloperidol, while neutralization of Met-enkephalin induced Straub tail response by means of Peptide-D indicated the presence of new non-opioid (naloxone independent) receptor system containing Peptide-D sequence (calpastatin 201-205 aa)
