Cholinergic stimulation of pancreatic polypeptide release by a meal, bombesin, neurotensin, tetragastrin, cholecystokinin, and cerulein

Abstract

It has been demonstrated that pancreatic polypeptide (PP) release can be markedly impaired by vagotomy or anticholinergic drugs. The current studies examine the role of cholinomimetic stimulation on PP release in dogs. Eight conscious animals underwent a series of tests: (1) a test meal (10 g/kg Alpo); (2) tetragastrin infusion (4 micrograms/kg/hr); (3) bombesin infusion (1.0 microgram/kg/hr); (4) cerulein infusion (100 ng/kg/hr); (5) cholecystokinin octapeptide (CCK-OP) infusion (100 ng/kg/hr); (6) neurotensin infusion (3 ng/kg/hr). All the studies were repeated individually with intravenous bethanecol (100 micrograms/kg/hr) as the background stimulant. The mean increment of PP released by a meal (160 +/- 32 fmol/ml) was significantly increased by bethanecol infusion (316 +/- 49 fmol/ml) (P less than 0.05). Each individual peptide released a significant amount of PP; tetragastrin: 53 +/- 11; neurotensin: 58 +/- 14; CCK-OP: 42 +/- 9; cerulein: 42 +/- 12; bombesin: 118 +/- 24 (P less than 0.05). Bethanecol did not significantly augment PP release by any of the individual peptides (P greater than 0.05). This study indicates that PP release by a meal is sensitive to cholinomimetic stimulation and that the peptide involved is neither gastrin, neurotensin, CCK, bombesin, nor cerulein. These data support the possibility of the existence of a cholinergic stimulatable mechanism, possibly a peptide responsible for the release of PP.