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Gene Review

NTS  -  neurotensin

Homo sapiens

Synonyms: NMN-125, NN, NT, NT/N, NTS1, ...
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Disease relevance of NTS


Psychiatry related information on NTS


High impact information on NTS


Chemical compound and disease context of NTS

  • BON cells, a novel human carcinoid cell line that produces and secretes NT peptide and expresses the gene encoding NT (designated NT/N), were treated with ethidium bromide (EB; 0.05, 0.1, and 0.4 microg/ml), an inhibitor of DNA and RNA synthesis, or vehicle over a time course (1-4 days) [4].
  • A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development [16].
  • Stimulation of vasoactive intestinal peptide and neurotensin secretion by pentagastrin in a patient with VIPoma syndrome [17].
  • To characterize the properties of the antibody fragment, human and rat high-affinity neurotensin receptors were expressed in E. coli in functional form, linked at their N-termini to the maltose-binding protein [18].
  • The gene encoding the gut hormone neurotensin/neuromedin N (NT/N) is expressed in the adult small bowel, and NT/N is transiently expressed in the fetal liver, suppressed in the adult liver, and reexpressed in certain liver cancers [19].

Biological context of NTS

  • Using PANC-1 as a model system, we demonstrate that neurotensin (NT) induced a rapid and striking activation of PKD as determined by in vitro kinase assay and by in vivo phosphorylation of serines 744, 748, and 916 [20].
  • Whether the NT expressing neurons play a role in generating circadian rhythms in the early life of humans needs to be further investigated [21].
  • Recombinant hNT1-R-producing cells, which lacked the endogenous G-protein-coupled receptor for the alpha pheromone, mated with wild-type MATalpha haploid cells in response to neurotensin, leading to bona fide diploid zygote formation [22].
  • We now confirm this assignment and place the NTS gene on the physical and cytogenetic maps [23].
  • The NTS gene is located on a yeast artificial chromosome contig that contains several polymorphic markers and is close to a polymorphic marker located at 95.8 cM on the Généthon linkage map [23].

Anatomical context of NTS

  • Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1 [20].
  • NT induced a rapid and transient translocation of PKD from the cytosol to the plasma membrane [20].
  • OBJECTIVE: The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland [24].
  • Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines [25].
  • NT terminal plexuses were particularly abundant in layers I-VI of the anterior cingulate cortex, in layer I of area 32 and of medical areas 9, 8, 6 and in layers II-III of area 29, of the presubiculum and entorhinal cortex [25].

Associations of NTS with chemical compounds

  • PKD activation induced by NT was abrogated by treatment of PANC-1 cells with PKC inhibitors GF-1 and Ro 31-8220 [20].
  • Rho protein inhibitor C3 dramatically inhibited both NT secretion and PKD activity [26].
  • In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m [24].
  • Competition binding studies of neurotensin with SR142948 and SR48692, two nonpeptidic antagonists of hNT1-R, indicated that the yeast-produced recombinant receptor displayed the same pharmacological properties as hNT1-R expressed in mammalian cells [22].
  • Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus [21].

Physical interactions of NTS


Enzymatic interactions of NTS


Regulatory relationships of NTS

  • Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor [22].
  • Furthermore, inhibition of PKC-alpha and -delta blocked PMA-stimulated NT secretion, suggesting a critical role for these isoforms in NT release [30].
  • These results indicate that modulation of tyrosine hydroxylase gene expression may constitute one of the mechanisms involved in the control of dopamine transmission by neurotensin [31].
  • We speculate that a complex pattern of regulation requiring interaction between a proximal CRE/AP-1-like motif and other upstream control elements play an important role in the high-level constitutive expression of NT/N in the human endocrine cell line BON [32].
  • Cell stimulation with the GPCR agonist neurotensin induced a rapid and reversible plasma membrane translocation of PKD3 that is PKC-dependent [33].

Other interactions of NTS

  • No significant intergroup differences were noted in postprandial levels of Nt and CCK [34].
  • Collectively our results demonstrate, for the first time, the existence of a functional PKC/PKD signaling pathway in human ductal pancreatic carcinoma cells and suggest that PKCs mediate the mitogenic signaling process initiated by NT [20].
  • BBS-mediated NT secretion was attenuated by MARCKS siRNA [35].
  • A few varicose fibers were labeled with antisera against neurotensin (NT), leucine-enkephalin (L-ENK), and the vasoactive intestinal polypeptide (VIP) [36].
  • Even in zones where TH and NT innervations were abundant, such as the anterior cingulate cortex or area 32, double-labeling procedures disclosed no colocalized fibers [25].

Analytical, diagnostic and therapeutic context of NTS

  • HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts [24].
  • We expressed the intracellular receptor NTR3 as a soluble protein secreted into the cell culture medium, which allowed characterization of its R-NT and neurotensin binding properties [1].
  • Intravenous infusion of neurotensin produced dilatation of the gallbladder (from a mean basal volume of 13.7 +/- 2.3 cc to 20.0 +/- 1.8 cc) [2].
  • We determined the effects of infused neurotensin (4 pmol/kg-min) on gallbladder contractility, measured by ultrasonography in 10 adult volunteers, and we evaluated release of neurotensin in eight patients with gallstones [2].
  • Measurement of immunoreactive peptide levels with radioimmunoassay, and visualization of peptidergic neurons and fibers with immunocytochemistry has demonstrated not only that peptides exist in the vicinity of A10 dopamine neurons, but using double labeling techniques NT and CCK have been found to coexist with dopamine in the same neuron [37].


  1. A novel form of neurotensin post-translationally modified by arginylation. Eriste, E., Norberg, A., Nepomuceno, D., Kuei, C., Kamme, F., Tran, D.T., Strupat, K., Jörnvall, H., Liu, C., Lovenberg, T.W., Sillard, R. J. Biol. Chem. (2005) [Pubmed]
  2. The role of neurotensin in human gallbladder motility. Walker, J.P., Khalil, T., Wiener, I., Fagan, C.J., Townsend, C.M., Greeley, G.H., Thompson, J.C. Ann. Surg. (1985) [Pubmed]
  3. Neuropeptides as autocrine growth factors in cancer cells. Moody, T.W., Chan, D., Fahrenkrug, J., Jensen, R.T. Curr. Pharm. Des. (2003) [Pubmed]
  4. Inhibition of mitochondrial gene transcription suppresses neurotensin secretion in the human carcinoid cell line BON. Li, N., Wang, Q., Li, J., Wang, X., Hellmich, M.R., Rajaraman, S., Greeley, G.H., Townsend, C.M., Evers, B.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  5. Neurotensin counteracts apoptosis in breast cancer cells. Somaï, S., Gompel, A., Rostène, W., Forgez, P. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  6. Mutational analysis of neurotensin in familial restless legs syndrome. Desautels, A., Turecki, G., Xiong, L., Rochefort, D., Montplaisir, J., Rouleau, G.A. Mov. Disord. (2004) [Pubmed]
  7. Plasma cholecystokinin and neurotensin after an ordinary meal in humans. A prolonged time study. Gullo, L., Pezzilli, R., Tomassetti, P., de Giorgio, R. Gastroenterol. Clin. Biol. (1998) [Pubmed]
  8. Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns. Näslund, E., Melin, I., Grybäck, P., Hägg, A., Hellström, P.M., Jacobsson, H., Theodorsson, E., Rössner, S., Backman, L. Am. J. Clin. Nutr. (1997) [Pubmed]
  9. Comparison of the nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) and half-hourly cigarette smoking. Gupta, S.K., Hwang, S.S., Causey, D., Rolf, C.N., Gorsline, J. Journal of clinical pharmacology. (1995) [Pubmed]
  10. Regional brain concentrations of neuropeptides in Huntington's chorea and schizophrenia. Nemeroff, C.B., Youngblood, W.W., Manberg, P.J., Prange, A.J., Kizer, J.S. Science (1983) [Pubmed]
  11. Perspective: National Cancer Institute summary report about estimated exposures and thyroid doses received from iodine 131 in fallout after Nevada atmospheric nuclear bomb tests. Hundahl, S.A. CA: a cancer journal for clinicians. (1998) [Pubmed]
  12. Co-localization of neurotensin-like immunoreactivity and 3H-glycine uptake system in sustained amacrine cells of turtle retina. Weiler, R., Ball, A.K. Nature (1984) [Pubmed]
  13. Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Iversen, L.L., Iversen, S.D., Bloom, F., Douglas, C., Brown, M., Vale, W. Nature (1978) [Pubmed]
  14. Peptide receptors as molecular targets for cancer diagnosis and therapy. Reubi, J.C. Endocr. Rev. (2003) [Pubmed]
  15. Neurotensin and dopamine interactions. Binder, E.B., Kinkead, B., Owens, M.J., Nemeroff, C.B. Pharmacol. Rev. (2001) [Pubmed]
  16. Imaging tumors with peptide-based radioligands. Behr, T.M., Gotthardt, M., Barth, A., Béhé, M. The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR). (2001) [Pubmed]
  17. Stimulation of vasoactive intestinal peptide and neurotensin secretion by pentagastrin in a patient with VIPoma syndrome. Brunt, L.M., Mazoujian, G., O'Dorisio, T.M., Wells, S.A. Surgery (1994) [Pubmed]
  18. Characterization of an antibody Fv fragment that binds to the human, but not to the rat neurotensin receptor NTS-1. Grisshammer, R., Grunwald, T., Sohal, A.K. Protein Expr. Purif. (2002) [Pubmed]
  19. DNA methylation contributes to expression of the human neurotensin/neuromedin N gene. Dong, Z., Wang, X., Zhao, Q., Townsend, C.M., Evers, B.M. Am. J. Physiol. (1998) [Pubmed]
  20. Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1. Guha, S., Rey, O., Rozengurt, E. Cancer Res. (2002) [Pubmed]
  21. Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus. Xu, H., Hu, X.Y., Wu, L., Zhou, J.N. Neurosci. Lett. (2003) [Pubmed]
  22. Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor. Leplatois, P., Josse, A., Guillemot, M., Febvre, M., Vita, N., Ferrara, P., Loison, G. Eur. J. Biochem. (2001) [Pubmed]
  23. Physical mapping of the human neurotensin gene (NTS) between markers D12S1444 and D12S81 on chromosome 12q21. Marondel, I., Renault, B., Lieman, J., Ward, D., Kucherlapati, R. Genomics (1996) [Pubmed]
  24. The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells. Sicard, F., Contesse, V., Lefebvre, H., Ait-Ali, D., Gras, M., Cartier, D., Decker, A., Chartrel, N., Anouar, Y., Vaudry, H., Delarue, C. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  25. Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines. Gaspar, P., Berger, B., Febvret, A. Brain Res. (1990) [Pubmed]
  26. The role of protein kinase D in neurotensin secretion mediated by protein kinase C-alpha/-delta and Rho/Rho kinase. Li, J., O'Connor, K.L., Hellmich, M.R., Greeley, G.H., Townsend, C.M., Evers, B.M. J. Biol. Chem. (2004) [Pubmed]
  27. Activation of mitogen-activated protein kinase couples neurotensin receptor stimulation to induction of the primary response gene Krox-24. Poinot-Chazel, C., Portier, M., Bouaboula, M., Vita, N., Pecceu, F., Gully, D., Monroe, J.G., Maffrand, J.P., Le Fur, G., Casellas, P. Biochem. J. (1996) [Pubmed]
  28. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Donoghue, M., Hsieh, F., Baronas, E., Godbout, K., Gosselin, M., Stagliano, N., Donovan, M., Woolf, B., Robison, K., Jeyaseelan, R., Breitbart, R.E., Acton, S. Circ. Res. (2000) [Pubmed]
  29. Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase. Lim, E.J., Sampath, S., Coll-Rodriguez, J., Schmidt, J., Ray, K., Rodgers, D.W. J. Biol. Chem. (2007) [Pubmed]
  30. Phorbol ester-mediated neurotensin secretion is dependent on the PKC-alpha and -delta isoforms. Li, J., Hellmich, M.R., Greeley, G.H., Townsend, C.M., Evers, B.M. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  31. Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP212 cells. Najimi, M., Hermans, E., Rostène, W., Forgez, P. Metabolic brain disease. (2001) [Pubmed]
  32. Characterization of promoter elements required for cell-specific expression of the neurotensin/neuromedin N gene in a human endocrine cell line. Evers, B.M., Wang, X., Zhou, Z., Townsend, C.M., McNeil, G.P., Dobner, P.R. Mol. Cell. Biol. (1995) [Pubmed]
  33. Protein kinase C nu/protein kinase D3 nuclear localization, catalytic activation, and intracellular redistribution in response to G protein-coupled receptor agonists. Rey, O., Yuan, J., Young, S.H., Rozengurt, E. J. Biol. Chem. (2003) [Pubmed]
  34. Postprandial levels of prolactin and gut hormones in breast cancer patients: association with stage of disease, but not dietary fat. Goettler, D.M., Levin, L., Chey, W.Y. J. Natl. Cancer Inst. (1990) [Pubmed]
  35. Myristoylated alanine-rich C kinase substrate-mediated neurotensin release via protein kinase C-delta downstream of the Rho/ROK pathway. Li, J., O'Connor, K.L., Greeley, G.H., Blackshear, P.J., Townsend, C.M., Evers, B.M. J. Biol. Chem. (2005) [Pubmed]
  36. Neurotransmitters, receptors, and neuropeptides in the accessory optic system: an immunohistochemical survey in the pigeon (Columba livia). Britto, L.R., Hamassaki, D.E., Keyser, K.T., Karten, H.J. Vis. Neurosci. (1989) [Pubmed]
  37. Interactions between neuropeptides and dopamine neurons in the ventromedial mesencephalon. Kalivas, P.W. Neuroscience and biobehavioral reviews. (1985) [Pubmed]
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