Cytoprotective effect of centrally administered neurotensin on stress-induced gastric ulcers.
Neurotensin, a peptide common to brain and gastrointestinal tissue, has been reported common to brain and gastrointestinal tissue, has been reported to inhibit both gastric acid secretion and gastric mucosal blood flow after central nervous system administration in rats. Therefore, the effect of intracisternal neurotensin on the development of gastric ulcers induced by cold-plus-restraint stress in the rat was studied. Following intracisternal injection, neurotensin (20-30 micrograms) significantly inhibited the development of gastric ulcers in this model. This effect was shown to be both dose related and route specific, inasmuch as neither lower doses of intracisternal neurotensin nor intravenous neurotensin were cytoprotective. In addition, potential actions of central neurotensin that may have mediated this beneficial effect were tested by administering somatostatin or oxotremorine intracisternally and cimetidine or haloperidol intraperitoneally. In contrast to intracisternal neurotensin, none of these substances reduced the incidence of gastric ulcers in this model. This was true despite the fact that cimetidine, but not neurotensin, significantly increased gastric pH. Finally, when cold-plus-restraint-stressed rats were pretreated with indomethacin, an inhibitor of prostaglandin synthesis, the cytoprotective effect of neurotensin was completely abolished. These results suggest that intracisternal neurotensin exerts a significant cytoprotective effect for stress-induced gastric ulcers in rats. This effect, which is mediated by the central nervous system, does not appear to be related to changes in body temperature, neuroleptic-like properties, or gastric acid secretion but requires an intact prostaglandin synthetic pathway.
D000818:Animals; D002927:Cimetidine / Q000627:therapeutic use; D003080:Cold Temperature; D005508:Food Deprivation; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006220:Haloperidol / Q000627:therapeutic use; D008297:Male; D009496:Neurotensin / Q000627:therapeutic use*; D010095:Oxotremorine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013004:Somatostatin / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*
D009496:Neurotensin; D013004:Somatostatin; D010095:Oxotremorine; D002927:Cimetidine; D006220:Haloperidol