The localization of the site(s) of neurotensin release in man and dog

Abstract

AbstractThe major source of neurotensin in the gut is the ‘N’ cell and this is found in the highest density in the ileum. The ingestion of food, particularly fat, causes the biphasic release of neurotensin‐like immunoreactivity (NTLI) into the circulation. The early peak occurs sooner than expected if it is due to the presence of chyme in the ileum, suggesting that the early release of neurotensin is due to a more proximal concentration of N cells or that neurotensin is released from the ileum by a more proximal stimulus. This paper investigates the site(s) of neurotensin release by studying: three groups of patients with various resections of the small intestine and the fashioning of duodenostomies, jejunostomies and ileostomies; and the dog with chronic gastric, duodenal and ileal fistulae, and following ileal resection. The results indicate that the jejunum and ileum are critical in the release of neurotensin following fat stimulation and that the stomach and duodenum have no direct role. The stimulation of the jejunum by fat causes the early rise of plasma NTLI by releasing neurotensin from the ileum. If chyme is prevented from passing to the distal jejunum the magnitude of the early peak is diminished and the second, later, peak is abolished. The second peak of plasma NTLI is due to the direct luminal stimulation of the distal jejunum and ileum by the products of fat digestion. Ileal resection completely abolishes any release of plasma NTLI in response to fat. It was concluded that the source of neurotensin released by the ingestion of food is the ileum. The release of neurotensin from the distal gut is dependent upon a signal from the proximal to the distal gut. The identity of the signal is unknown, but it is either neural or humoral and previous studies suggest a cholinergic‐dependent reflex.