Peptide YY inhibits meal-stimulated pancreatic and gastric secretion

Peptide YY was recently isolated from porcine intestine and shown to exhibit marked structural homology with pancreatic polypeptide, a potent inhibitor of pancreatic exocrine secretion. We have examined the effects of infused peptide YY on gastric and pancreatic secretion in four mongrel dogs with gastric and pancreatic fistulas. A 15% liver extract meal was instilled intragastrically, and normal saline or one of three doses of peptide YY (200, 400, and 800 pmol X kg-1 X h-1) was infused into a peripheral vein. All three doses of peptide YY significantly inhibited meal-stimulated pancreatic fluid and bicarbonate secretion, with the lowest dose inhibiting secretion by 44.5 +/- 3.5 and 53.6 +/- 8.5%, respectively. Pancreatic protein secretion and gastric acid secretion were significantly inhibited by the two highest doses. The 200, 400, and 800 pmol X kg-1 X h-1 doses of peptide YY were associated with increments in peripheral blood of 201 +/- 24, 357 +/- 50, and 971 +/- 139 pM, respectively. These values compared with mean increments of 86.3 +/- 8.5 pM after a meat meal and 403 +/- 63 pM after intestinally perfused oleic acid. The present studies demonstrate that peptide YY inhibits gastric and pancreatic secretion and suggest that peptide YY may be the gastric and pancreatic inhibitor in ileocolonic mucosa that is released by perfusion of the intestine with oleic acid.