INHIBITION OF RAT PANCREATIC EXOCRINE SECRETION BY NEUROPEPTIDE-Y - STUDIES INVIVO AND INVITRO

Neuropeptide Y (NPY) is a unique 36 amino acid peptide with strong sequence homology to pancreatic polypeptide and peptide YY. In the rat pancreas, NPY-positive fibers have been demonstrated in close association with exocrine structures, suggesting a regulatory role for the peptide. In conscious rats with pancreatic ductal cannulas, amylase output stimulated by cholecystokinin octapeptide (CCK-8: 0.2-mu-g kg-1 h-1) was dose-dependently inhibited by intravenous NPY infusion (20, 40, and 80-mu-g kg-1 h-1). Inhibitory effects were rapid in onset but reversed with cessation of NPY infusion. With continuous NPY infusion (40-mu-g kg-1 h-1), prolonged inhibition of amylase output by the vagal stimulant 2-deoxyglucose (100 mg kg-1) was observed (> 50% inhibition in each of nine consecutive 10-min periods). In contrast, NPY infusion in doses of 20, 40, or 80-mu-g kg-1 h-1 produced no alteration in immunoreactive somatostatin levels. In vitro, NPY incubation (10(-13)-10(-8) M) produced no change in basal amylase release from dispersed, purified acinar cells. In addition, co-incubation of NPY (10(-8)-10(-6) M) with CCK-8 (10(-13)-10(-8) M) produced no inhibition of CCK-stimulated amylase release from dispersed acini. In contrast, NPY (10(-6) M) produced significant inhibition of amylase release from pancreatic lobules that had been stimulated by 75 mM potassium (135 +/- 11% versus 177 +/- 18% of basal level) or by 25-mu-M veratridine (196 +/- 19% versus 398 +/- 152%). NPY is a potent inhibitor of pancreatic exocrine secretion in the rat in vivo and in pancreatic lobules in vitro. The actions of NPY are exerted indirectly and do not involve circulating somatostatin. Inhibition of pancreatic neurotransmission may be involved in the actions of NPY on the exocrine pancreas.