The effect of centrally administered neuropeptides on the development of stress-induced gastric ulcers in rats.
Neurotensin (NT) and bombesin, which are heterogeneously distributed in both brain and gastrointestinal tissue of several mammalian species, inhibit the formation of stress-induced gastric ulcers in rats. Many other endogeneous neuropeptides have also been reported to be present in brain and gastrointestinal tissue. The present study was conducted to evaluate the effect of some of these peptides on the development of cold-restraint stress (CRS)-induced gastric ulcers in rats. In addition, the effect of thyrotropin-releasing hormone (TRH), which antagonizes many of the CNS effects of NT, was investigated to determine whether this tripeptide antagonizes the cytoprotective effect of NT in this CRS model. All peptides were initially administered intracisternally (ic) in doses equimolar to 30 micrograms NT. As previously reported, NT (30 micrograms, ic) completely prevented the development of gastric ulcers in rats exposed to three hours of CRS. Bombesin, beta-endorphin, substance P, and somatostatin also exhibited cytoprotective activity. Several other peptides studied in the CRS model exerted no significant effects on the development of gastric ulcers; these included cholecystokinin octapeptide, gastrin, leu-enkephalin, met-enkephalin, and bradykinin. Two peptides, vasoactive intestinal polypeptide and TRH, significantly increased the severity of gastric ulcerations. The cytoprotective effect of NT was dose dependent. In contrast, lower doses of beta-endorphin, substance P, and somatostatin were cytoprotective whereas higher doses were not. Finally, concomitant ic injections of TRH antagonized the cytoprotective effects of NT and bombesin, but not that of beta-endorphin. The present results suggest that certain brain peptides may participate in modulating the gastric mucosal barrier, thereby increasing or decreasing its vulnerability to stress-induced lesions.
D000818:Animals; D001839:Bombesin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000627:therapeutic use; D008297:Male; D009496:Neurotensin / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage; D001615:beta-Endorphin
D004723:Endorphins; D010455:Peptides; D009496:Neurotensin; D013973:Thyrotropin-Releasing Hormone; D001615:beta-Endorphin; D001839:Bombesin