Inhibition of rat pancreatic exocrine secretion by neuropeptide Y: studies in vivo and in vitro.
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 microgram kg - 1 h -1) was dose-dependently inhibited by intravenous NPY infusion (20, 40, and 80 micrograms kg-1 h-1). Inhibitory effects were rapid in onset but reversed with cessation of NPY infusion. With continuous NPY infusion (40 microgram kg-1 h-1), prolonged inhibition of amylase output by the vagal stimulant 2-deoxyglucose (100 mg kg-1) was observed (greater than 50% inhibition in each of none consecutive 10-min periods). In contrast, NPY infusion in doses of 20, 40, or 80 micrograms 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 microM veratridine (196 +/- 19% versus 398 +/- 152%).(ABSTRACT TRUNCATED AT 250 WORDS)
Mulholland
M W
MW
Department of Surgery, Michigan Gastrointestinal Peptide Center, University of Michigan, Ann Arbor.
Lally
K
K
Taborsky
G J
GJ
D000681:Amylases / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007515:Islets of Langerhans / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D010179:Pancreas / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000097:blood; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D009478:Neuropeptide Y; D013779:Tetrodotoxin; D013004:Somatostatin; D014701:Veratridine; D003847:Deoxyglucose; D000681:Amylases; D012844:Sincalide