Role of neurotensin in the regulation of exocrine pancreatic secretion in dogs

Abstract

A potential physiological function of the regulatory gastrointestinal peptide neurotensin (NT) is the stimulation of exocrine pancreatic secretion. We investigated therefore whether immunoneutralization of the postprandially circulating peptide, intravenous application of either atropine or the highly specific CCK receptor antagonist, L-364,718, could influence neurotensin-mediated pancreatic secretion in dogs. The use of CCK receptor antagonist (0.1 mg kg −1 intraduodenally) inhibited postprandial and NT-mediated exocrine pancreatic secretion. The integrated postprandial protein secretion fell from 31 ± 1.6 to 23 ± 2.1 g 180 min −1 while the corresponding values in response to i.v.-NT (postprandial neurotensin concentration course was imitated by the infusion of 50 pmol kg h −1 NT) fell from 22 ± 1.9 to 7.5 ± 0.8 g 180 min −1. Immunoneutralization of postprandial NT led to a simultaneous significant reduction in postprandial pancreatic secretion (integrated protein release 31 ± 1.6 and 15.5 ± 1.4 g 180 min −1 respectively). The i.v. application of atropine lowered NT-mediated pancreatic secretion (e.g., protein output) from 22 ± 1.9 to 7.1 ± 7.1 ± 0.9 g 180 min −1. We conclude that NT plays an important role in the endocrine regulation of exocrine pancreatic secretion. This influence could be mediated by a CCK-dependent cholinergic mechanism.