Pharmacological evidence of morphine-induced inhibition of gastric mucus synthesis in rats.

The effects of morphine, administered at graded doses by either intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) routes, have been investigated on acid and pepsin outputs, secretory volume, ulcer score, free and bound gastric mucus, in pylorus-ligated rats. Morphine i.c.v. induced a dose-dependent inhibition of secretory volume, acid and pepsin outputs and ulcer score, without modification of either free or bound mucoproteins. Naloxone i.c.v. had no effect per se, but prevented the inhibitory effects of i.c.v. morphine. Morphine i.p. produced a dose-dependent inhibition of gastric secretory volume, acid and pepsin outputs, as well as both free and wall-bound mucoproteins. By contrast, the effect of i.p. morphine on ulcer score was not dose-dependent: the dose of 5 mg/kg induced significant exacerbation of gastric lesions. Naloxone at 0.8 mg/kg i.p. had no effect per se, whereas at the dose of 4 mg/kg it significantly increased bound gastric mucus. The dose of 0.8 mg/kg antagonized the effects of morphine on gastric secretory volume, acidity, pepsin and ulcer score, but not on gastric mucus. These results indicate that morphine affects gastric acidity through central and peripheral opiate receptors, whereas gastric mucus synthesis appears to be regulated through peripheral opioid pathways.