Central and peripheral sites of action for the protective effect of opioids of the rat stomach.

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.