EFFECTS OF NEUROPEPTIDE-Y AND [LEU(31),PRO(34)] 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 s elective NPY, receptor agonist, leucine31 proline34 neuropeptide Y ([l eu31,pro34]NPY) on gastric lesion formation and gastric secretion in t hree preparations: Basal gastric acid secretion in conscious rats, res traint-induced gastric lesion formation and acid and pepsin output and gastric mucosal damage in pylorus-ligated rats. The hypothesis that b enextramine, a non-selective NPY receptor antagonist, could attenuate responses to NPY or [leu31,pro34]NPY was also tested. Both NPY and [le u31,pro34]NPY (i.p. and i.c.v.) decreased basal gastric acid output, r estraint-induced gastric lesion formation, and acid and pepsin secreti on and gastric mucosal damage in pylorus-ligated rats. The magnitude o f inhibition of secretion and of ulcer reduction was significantly gre ater for [leu31,pro34]NPY than for NPY at comparable doses. Benextrami ne blocked the protective effect of NPY and [leu31,pro34]NPY against r estraint-induced gastric mucosal injury. Both central and peripheral t reatment with benextramine blocked the antisecretory effects of centra lly administered NPY and [leu31,pro34]NPY. These data were consistent with both a central and a peripheral action of NPY on the gut, possibl y through Y1 receptors.