The Site of Action of Neurotensin in the Rat Pancreas

The tridecapeptide neurotensin, present in endocrine cells of the ileal mucosa and in nerve bodies of cerebral nuclei, may play a role in the physiology of exocrine pancreatic regulation. This assumption is based on two observations: Neurotensin appears in the blood stream after a fatty meal and neurotensin stimulates exocrine pancreatic secretion. There has, however, been controversy on the site of action of this peptide since some investigators did not observe an effect on the pancreas in vitro and suggested, therefore, an indirect, perhaps neural or even central site of action. In the present investigation, we compared the action of neurotensin on the exocrine pancreas in vivo in the anesthetized rat after intracerebroventricular (i.c.v.) injection and after i.v. infusion and in vitro after incubation of the pancreas in three different preparations: isolated dispersed acini, isolated lobuli, and isolated total pancreas. We found that i.c.v. application of neurotensin stimulated exocrine pancreatic secretion only when doses were applied that led to elevated peripheral plasma neurotensin levels. In vitro, the action of neurotensin was very weak and the optimal dose was integrity dependent; e.g., a concentration of 10(-4) and 10(-5) M neurotensin was necessary to stimulate amylase release from isolated acini, 10(-8) M neurotensin induced amylase release from isolates lobuli, and 10(-9) M neurotensin released amylase from the intact pancreas. Intravenously, neurotensin resulted in a greater amylase release over basal than in any of the in vitro experiments. We conclude that neurotensin acts directly on the pancreatic acini but that the sensitivity of the pancreas is greatly enhanced when the organ is intact and has normal neural and vascular communications.(ABSTRACT TRUNCATED AT 250 WORDS)