Inhibitory action of peptide YY on pancreatic secretion is independent of secretin

The purpose of this study was to characterize the effect of peptide YY (PYY) on acid-stimulated pancreatic bicarbonate secretion and to determine whether PYY affects the release of secretin in response to intraduodenal infusion of acid. Six dogs were prepared with gastric and pancreatic cannulas. In study 1, graded doses of hydrochloric acid (HCl) (3, 6, 12, and 24 mEq/h) were given intraduodenally alone or in combination with intravenous PYY (400 pmol/kg•h). In study II, and ED₅₀ of intraduodenal HCl (6 mEq/h) was given alone or in combination with graded doses of PYY (12.5, 25, 50, 100, 200, and 400 pmol/kg•h, I.V.). Bicarbonate output was significantly inhibited during PYY infusion at 200 and 400 pmol/kg•h, but plasma secretin levels were unchanged. The calculated maximal response for bicarbonate secretion (5.1 ± 1.3 mEq/15 min) was significantly reduced by PYY (2.1 ± 0.7 mEq/15 min). We concluded that PYY can inhibit acid-stimulated pancreatic bicarbonate secretion without affecting the release of secretin. The mechanism of the inhibitory effect of PYY on acid-stimulated pancreatic bicarbonate secretion is compatible with a noncompetitive type of inhibition.