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.
Penner
S B
SB
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Smyth
D D
DD
Glavin
G B
GB
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D007103:Immobilization; D008026:Ligation; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D010434:Pepsin A / Q000378:metabolism; D011708:Pylorus / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000502:physiology; D013270:Stomach / Q000473:pathology; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications
D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C062259:neuropeptide Y, Leu(31)-Pro(34)-; C029998:benextramine; D010434:Pepsin A; D003538:Cystamine