PYY potently inhibits pancreatic exocrine secretion mediated through CCK-secretin-stimulated pathways but not 2-DG-Stimulated pathways in awake rats

Peptide YY (PYY) is an important modulator of stimulated pancreatic exocrine secretion. PYY acts proximal to the acinar cell but the exact site and mechanism of action are unknown. The aim of the present study is to determine the pathway through which PYY exerts its effect on the exocrine pancreas in awake rats under physiological condition. When pancreatic secretion was stimulated by graded doses of cholecystokinin (CCK) (14, 28, 58 pmol/kg/hr) with secretin (1.25, 2.5, 5.0 pmol/kg/hr) or CCK alone at 28 pmol/kg/hr, PYY1-36 dose-dependently inhibited pancreatic secretory responses. Moreover, PYY1-36 at 50 pmol/kg/hr almost completely blocked the stimulation by CCK (P < 0.01). Although background infusion of PYY1-36 or PYY3-36 at 12.5 pmol/kg/hr inhibited basal pancreatic fluid and protein secretion, but both of them only partly inhibited the subsequent 2-DG stimulated pancreatic fluid and protein secretion. Furthermore, PYY1-36 at 50 pmol/kg/hr failed to inhibit 2-DG-stimulated pancreatic secretion. These results confirm that PYY1-36 inhibits CCK-stimulated pancreatic secretion under all experimental conditions. However, in the awake, surgically recovered rat, PYY1-36 at both low and high doses failed to fully inhibit 2-DG-stimulated pancreatic secretion. Therefore, the site of PYY's inhibitory action on pancreatic secretion appears to be primarily on the CCK-stimulated pathway at a site proximal to the convergence of the CCK and 2-DG pathways.