d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Stomach-Ulcer

The effects of a synthetic Met-enkephalin analogue D-Ala2, MePhe4Met(O)5-ol]enkephalin (DAMME) (1 mg/kg. IP) on gastric damage produced by necrotizing agents (0.6 N HCl, ethanol 1 ml/rat, PO) were evaluated, and the correlation between histamine and opioids in stomach was investigated, Rats pretreated with DAMME bad significantly less severe lesions and lower histamine content in gastric tissue. The histamine level, expressed in mg/g of gastric tissue, changed from 0.41 +/- 0.10 of control animals to 1.33 +/- 0.12 for HCl and 1.51 +/- 0.20 for ethanol treatment, whereas in animals pretreated with DAMME the values were significantly reduced to 0.55 +/- 0.13 and 0.65 +/- 0.15. These results confirm a link between the gastroprotection produced by opioids and the modulation of histaminergic activity in the rat stomach.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enterochromaffin Cells; Gastric Mucosa; Histamine; Male; Mucus; Narcotics; Parietal Cells, Gastric; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Morphine and the synthetic opioid met-enkephalin analog [D-Ala2, MePhe4, Met(0)5ol] enkephalin (FK 33-824) injected intraperitoneally to rats at doses of 5-20 and 0.5-2 mg/kg respectively showed a protective effect on gastric lesion induced by cold-restraint stress. This protective effect was abolished by pretreatment with indomethacin. This suggests a role for prostaglandins in the protection, induced by opioids of the gastric mucosa against the development of stress-induced ulcers.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Gastric Mucosa; Indomethacin; Injections, Intraperitoneal; Male; Morphine; Narcotics; Prostaglandins; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological

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 N HCl or 0.2 N NaOH 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.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Gastric Mucosa; Hydrochloric Acid; Male; Morphine; Naltrexone; Rats; Rats, Inbred Strains; Sodium Hydroxide; Stomach Ulcer

The effects of morphine HCl and a synthetic met-enkephalin analogue [D-Ala2,MePhe4,Met(O)5ol]enkephalin (FK 33-824) on gastric damage produced by the intraperitoneal administration of indomethacin (10 mg/kg i.p.) have been investigated. Rats intraperitoneally pretreated with morphine HCl (10 mg/kg i.p.) and FK 33-824 (1 mg/kg i.p.) showed a statistically significant reduction both of the number and intensity of lesions induced by indomethacin. This protection was reversed by naloxone HCl (2 mg/kg i.p.). The protective effect was not related to a reduction of gastric secretion since the antisecretory drug cimetidine (25 mg/kg i.p.) and methscopolamine bromide (10 mg/kg i.p.) did not significantly prevent mucosal damage under the same experimental conditions.

Topics: Animals; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Indomethacin; Male; Morphine; Rats; Rats, Inbred Strains; Stomach Ulcer

Rats exposed to combined cold and restraint exhibited a reduced intensity of gastric damage when pre-treated intraperitoneally with morphine HCl or with the synthetic enkephalin analog [D-Ala2, MePhe4, Met(0)5ol]enkephalin (FK 33-824). Morphine HCl and FK 33-824 prevented some of the indices of the lesion also when injected intracerebroventricularly; morphine methyliodide, quaternary derivative of morphine with does not cross the blood brain barrier, was fully effective, by intraperitoneal route, in preventing the gastric damage. Both peripheral and central mechanisms seem, therefore, involved in the protective effect of opioids on rat gastric mucosa. Morphine HCl and FK 33-824 reduced significantly gastric acid secretion when administered intracerebroventricularly or intraperitoneally; in addition, a concomitant increase of prostaglandin production was observed in rat gastric mucosa after i.p. administration of both opioids. Both these events might contribute to the protective action of opioids on the stomach.

Topics: Animals; Brain; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Enkephalin, Methionine; Gastric Acid; Gastric Mucosa; Male; Morphine; Narcotics; Prostaglandins; Rats; Rats, Inbred Strains; Receptors, Opioid; Stomach; Stomach Ulcer