Peptide YY inhibits nutrient-, hormonal-, and vagally-stimulated pancreatic exocrine secretion

Peptide YY (PYY) is a recently isolated gut peptide that is found primarily in the mucosal endocrine cells of the terminal ileum, colon, and rectum of several mammalian species, including humans. The purpose of this study was to characterize the effect of PYY on pancreatic exocrine secretion in six conscious dogs prepared with pancreatic and gastric fistulas. In control experiments, pancreatic exocrine secretion was stimulated by either intravenous (i.v.) administration of secretin (100 ng/kg/h), cholecystokinin-8 (50 ng/kg/h), neurotensin (5 micrograms/kg/h), or 2-deoxy-D-glucose (75 mg/kg); or by the intraduodenal infusion of hydrochloric acid (4 mEq/h), a mixture of amino acids (phenylalanine + tryptophan at 5 mmol/h), sodium oleate (9 mmol/h), or a liquid meal. On separate days, PYY (12.5, 25, 50, 100, 200, or 400 pmol/kg/h) was given intravenously in combination with one of the above pancreatic secretagogues. Intravenous PYY at 200 and 400 pmol/kg/h inhibited secretin-stimulated pancreatic bicarbonate output significantly (p less than 0.05). Pancreatic bicarbonate and protein responses to all pancreatic secretagogues were reduced significantly (p less than 0.05) by PYY at 400 pmol/kg/h. Intravenous administration of atropine (0.6 mg bolus, followed by 0.02 mg/kg/h) did not abolish the ability of PYY to inhibit secretin-stimulated pancreatic bicarbonate secretion. This study demonstrates that PYY can inhibit nutrient-, hormonal-, and vagally-stimulated pancreatic exocrine secretion in the dog; its mechanism of action appears to be independent of cholinergic innervation.