Structural requirements of peptide YY for biological activity at enteric sites

Peptide YY (PYY) is a colonic hormone consisting of 36 amino acids that is a potent inhibitor of pancreatic exocrine, gastric acid, and insulin secretion. The objective of the present experiments was to characterize the structural requirements of PYY for inhibition of pancreatic exocrine, gastric acid, and insulin secretion, using conscious dogs prepared with gastric and pancreatic fistulas. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (400 pmol · kg^-1 · h^-1) inhibited cholecystokinin-8- stimulated (25 pmol · kg^-1 · h^-1) pancreatic exocrine secretion (P < 0.05); however, PYY-(1-10), PYY-(1-20), PYY-(6-36), PYY-(10-36), PYY-(13-36), PYY-(24-36), and PYY-(27-36) did not inhibit pancreatic exocrine secretion. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (200, 400, 800 pmol · kg^-1 · h^-1) inhibited pentagastrin (0.5 μg · kg^-1 · h^-1) -stimulated gastric acid secretion (P < 0.05), as well as 2-deoxy- D-glucose-stimulated insulin release (75 mg/kg) in a dose-related manner. PYY-(6-36), PYY-(13-36), and [Leu³¹, Pro³⁴]neuropeptide Y did not inhibit either gastric acid secretion or insulin release. In the gastric acid and insulin secretion bioassays, PYY-(1-36) was significantly more potent than PYY-(3-36) and PYY-(4-36); however, in the pancreatic exocrine secretion bioassay, the inhibitory effects of PYY-(3-36) and PYY-(1-36) did not differ significantly. PYY-(4-36) was less potent than PYY-(1-36) on pancreatic exocrine secretion. These results indicate that full expression of the inhibitory activity of PYY on gastric acid and insulin secretion requires the full sequence of PYY, whereas PYY-(3-36) is as effective as PYY-(1-36) in the inhibition of pancreatic exocrine secretion.