Effects of neuropeptide Y and [Leu31,Pro34] neuropeptide Y on experimental gastric lesion formation and gastric secretion in the rat.

The present study examined the effects of neuropeptide Y (NPY) and a selective NPY1 receptor agonist, leucine31 proline34 neuropeptide Y ([leu31,pro34]NPY) on gastric lesion formation and gastric secretion in three preparations: Basal gastric acid secretion in conscious rats, restraint-induced gastric lesion formation and acid and pepsin output and gastric mucosal damage in pylorus-ligated rats. The hypothesis that benextramine, a non-selective NPY receptor antagonist, could attenuate responses to NPY or [leu31,pro34]NPY was also tested. Both NPY and [leu31,pro34]NPY (i.p. and i.c.v.) decreased basal gastric acid output, restraint-induced gastric lesion formation, and acid and pepsin secretion and gastric mucosal damage in pylorus-ligated rats. The magnitude of inhibition of secretion and of ulcer reduction was significantly greater for [leu31,pro34]NPY than for NPY at comparable doses. Benextramine blocked the protective effect of NPY and [leu31,pro34]NPY against restraint-induced gastric mucosal injury. Both central and peripheral treatment with benextramine blocked the antisecretory effects of centrally administered NPY and [leu31,pro34]NPY. These data were consistent with both a central and a peripheral action of NPY on the gut, possibly through Y1 receptors.