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Neurotensin, a tridecapeptide, was originally isolated in the 1970s from bovine hypothalamus. J Biol Chem. 1973 Oct 10;248(19):6854-61.   It functions as a neurotransmitter in the brain, and as a hormone with paracrine actions in the gut.  The highest concentrations of Neurotensin has since been shown to occur in the gut, mostly in the ileum, with lower concentrations in the jejunum.  Klin Wochenschr. 1984 Jun 1;62(11):523-30.    Vagal and non-vagal mechanisms (via Bombesin) regulate Neurotensin release, with fat being the most potent stimulator of Neurotensin release. Endocrinology. 1985 Mar;116(3):1133-8.   Increased Neurotensin release has been described with alcohol  and Long chain fatty acids   J Nutr. 2002 Mar;132(3):329-32.   as well as  in patients undergoing jejuno-ileal bypass, and those with VIPomas.   Neurotensin release is inhibited by somatostatin. Three NT receptors, NTS1, NTS2 and NTS3, have been described,   Curr Opin Drug Discov Devel. 2002 Sep;5(5):764-76.    with NTS1 mediating most of the central and peripheral actions of Neurotensin.  

Neurotensin positive neurons have been identified in the hypothalamic nuclei, especially in the arcuate nucleus, PVN and DMN. Brain Res. 1984 Jun 8;302(2):221-30.  ob/ob mice have lower hypothalamic Neurotensin mRNA and Neurotensin levels as well as increased Neuropeptide Y expression.Endocrinology. 1993 May;132(5):1939-44   Zucker obese rats (fa/fa rats) have decreased Neurotensin concentration in the hypothalamic nuclei, Metabolism. 1995 Aug;44(8):972-5  suggesting an impaired processing of brain pro-Neurotensin.



 
Neurotensin Actions

Plasma levels of Neurotensin rise after a meal in lean subjects, predominantly in response to fat. Neurotensin decreases gastric emptying rate, with increased transit times through the intestine. But post-prandial Neurotensin levels are lower in the obese, probably as a secondary effect rather than a primary factor involved in altering intestinal transit. Neurotensin inhibits spontaneous and NE-induced feeding in rats. Central administration of Neurotensin has been shown to induce satiety and modulation of feeding behaviour.  Int Rev Neurobiol. 1985;27:207-98.   Whether Neurotensin has a role in day to day feeding remains to be clarified. Multiple functions have been attributed to Neurotensin including release of hormones from the pituitary   Neuropeptides. 1997 Feb;31(1):8-11.     J Pediatr Endocrinol Metab. 1998 Sep-Oct;11(5):615-21.   and gut (glucagon, insulin, somatostatin, pancreatic polypeptide), as well as roles in thermoregulation, Res Commun Mol Pathol Pharmacol. 1995 Mar;87(3):323-32.   increased vascular permeability and  vasodilatation,  Eur J Pharmacol. 1990 Jan 17;175(3):279-83.   inhibition of gastric acid secretion, Curr Top Med Chem. 2004;4(1):63-73.  stimulation of pancreatic secretion Pancreatology. 2001;1(4):320-35.   and modulation of gastric motility. Gastroenterology. 1990 Feb;98(2):517-28. Neurotensin may produce vasoconstrictor effect on the adipose tissue with implications on fat uptake and storage.  Ann N Y Acad Sci. 1982;400:183-97.   Neurotensinomas have been described with clinical features of oedema, hypotension, cyanosis and flushing. Semin Oncol. 1987 Sep;14(3):263-81.  Potential therapeutic uses for Neurotensin exists in the fields of cancer, pain relief, schizophrenia and Obesity.
Neurotensin related Peptides

Other Neurotensin-related peptides described include Neuromedin N, Xenopsin and Xenin. 

Xenin is a 25 amino acid peptide identified in the human gastric mucosa. J Biol Chem. 1992 Nov 5;267(31):22305-9     Xenin, produced from Pro-Xenin,  induces exocrine Peptides. 1998;19(3):609-15   and endocrine pancreatic secretion   Regul Pept. 2003 Aug 15;115(1):25-9.  with stimulation of insulin and glucagon release from the pancreas in invitro studies in rat pancreas.   Xenin also modulates small and large intestinal motility through interaction with the Neurotensin receptor, although  its physiological role remains unclear. A possible role in appetite regulation has been suggested by the suppressive effect on food intake in rats injected intracerebroventricularly with Xenin. Brain Res. 1998 Aug 3;800(2):294-9.