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Gene Review

Nts  -  neurotensin

Mus musculus

Synonyms: 5033428E16Rik, NMN-125, NN, NT, NT/N, ...
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Disease relevance of Nts

  • In addition, NT stimulates growth of certain colon cancers; the mechanism for this effect is not known [1].
  • Neurotensin (NT), a tridecapeptide, is a neurotransmitter that elicits potent effects including hypothermia and antinociception in mice and rats [2].
  • These findings show that the new NT peptide analogues are robust and can deliver imaging agents to NTR-positive tumors such as pancreatic cancer [3].
  • In vivo biodistribution of a representative (111)In-DTPA-NT peptide analogue in SCID mice bearing NTR-positive human adenocarcinoma (HT29) xenograft shows that the compound was primarily retained in tumor tissue (2.2% ID/g) and the kidneys (4.8% ID/g) at 4 h postinjection [3].
  • Colitis-induced body weight loss, colonic myeloperoxidase activity, and histological damage were significantly enhanced by SR-48642 administration, a nonpeptide NTR1 antagonist, whereas continuous NT infusion ameliorated colitis outcome [4].

Psychiatry related information on Nts

  • Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia [5].
  • In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in different behavioural tests of locomotor activity using vehicle, amphetamine, or haloperidol in mice [6].
  • These results illustrate the profound alterations in the NT system induced by chronic stimulation of DA receptors and underscore the potential clinical relevance of NT/DA interactions in schizophrenia and drug abuse [7].

High impact information on Nts


Chemical compound and disease context of Nts


Biological context of Nts

  • The pharmacological properties of this receptor correspond to those of the low-affinity, levocabastine-sensitive NT binding site described initially in membranes prepared from rat and mouse brain [15].
  • Murine neuroblastoma clone N1E-115 possesses receptors that specifically bind the tridecapeptide neurotensin, mediate the formation of intracellular cyclic GMP, and stimulate inositol phospholipid hydrolysis [16].
  • This decrease in Bmax is more likely to be a result of intracellular sequestration of recyclable NT receptors than of true down-regulation due to the rapid resensitization seen for the NT-mediated biological response [16].
  • In this study, we examined the effect of neurotensin on DARPP-32 Thr75 phosphorylation using mouse neostriatal slices [17].
  • A dose of 18 nmol of NT or NT27 caused a body temperature lowering of 1.8 and 1.2 degrees C, respectively [2].

Anatomical context of Nts

  • When the receptor is expressed in Xenopus laevis oocytes, the H1 antihistaminic drug levocabastine, like NT and neuromedin N, triggers an inward current [15].
  • Neurotensin/N mRNA transcripts were identified in all four of the HCC cell lines and in one of nine HCC in nude mice [1].
  • Neurotensin expression was found in two of six freshly resected HCC and in none of the six corresponding samples of normal mucosa [1].
  • In vitro, NT and NT-2 at 30 nM caused predominantly contraction and relaxation in isolated distal colon and proximal ileum, respectively, from +/+ mice, but no responses were observed with tissues from -/- mice [18].
  • We have identified a NT analog of the NT(8-13) fragment, NT27, that selectively causes only the hypothermic response in vivo, when microinjected into the periaqueductal gray (PAG) of rats [2].

Associations of Nts with chemical compounds


Physical interactions of Nts

  • Biochemical analysis and confocal microscopic imaging clearly indicate that NT is efficiently internalized after binding to NTR3, and that despite this internalization, the amount of receptor present on the cell surface is maintained [19].
  • Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth [3].
  • Radiolabeled ligands specific for the G protein-coupled state of neurotensin receptors [20].

Regulatory relationships of Nts

  • Leptin-induced NT regulation was attenuated by dominant-negative STAT3 protein expression [21].
  • We previously found that genetic or pharmacological manipulations that disrupt endogenous NT signaling attenuate antipsychotic drug-induced Fos expression in the dorsolateral and central striatum but not other striatal regions [22].
  • Inhibition of neurotensin-induced pancreatic carcinoma growth by a nonpeptide neurotensin receptor antagonist, SR48692 [23].
  • Finally a high expression of NTRL was evident in brainstem structures implicated in descending antinociceptive influences (e.g., the periaqueductal gray, nucleus raphe magnus, gigantocellular reticular nucleus, pars alpha, and lateral paragigantocellular nucleus) consistent with the proposed mediation of NT-induced analgesia by the NTRL [24].
  • Neurotensin (10 microM) exhibited no influence on adenylate cyclase activity, 45Ca uptake, or 32Pi incorporation into phosphatidylinositol fractions of NG108-15 cells [25].

Other interactions of Nts

  • Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor [26].
  • Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin [19].
  • In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception [27].
  • Leptin-mediated induction of NT gene expression was biphasic at 10(-11) and 10(-7) M [21].
  • Neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115 was decreased following prolonged exposure of intact cells to nondegraded neurotensin [16].

Analytical, diagnostic and therapeutic context of Nts


  1. Neurotensin expression and release in human colon cancers. Evers, B.M., Ishizuka, J., Chung, D.H., Townsend, C.M., Thompson, J.C. Ann. Surg. (1992) [Pubmed]
  2. Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception. Tyler, B.M., Cusack, B., Douglas, C.L., Souder, T., Richelson, E. Brain Res. (1998) [Pubmed]
  3. Novel bioactive and stable neurotensin peptide analogues capable of delivering radiopharmaceuticals and molecular beacons to tumors. Achilefu, S., Srinivasan, A., Schmidt, M.A., Jimenez, H.N., Bugaj, J.E., Erion, J.L. J. Med. Chem. (2003) [Pubmed]
  4. Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation. Brun, P., Mastrotto, C., Beggiao, E., Stefani, A., Barzon, L., Sturniolo, G.C., Palù, G., Castagliuolo, I. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  5. Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia. Remaury, A., Vita, N., Gendreau, S., Jung, M., Arnone, M., Poncelet, M., Culouscou, J.M., Le Fur, G., Soubrié, P., Caput, D., Shire, D., Kopf, M., Ferrara, P. Brain Res. (2002) [Pubmed]
  6. Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice. Casti, P., Marchese, G., Casu, G., Ruiu, S., Pani, L. Neuropharmacology (2004) [Pubmed]
  7. Altered neurotensin mrna expression in mice lacking the dopamine transporter. Roubert, C., Spielewoy, C., Soubrié, P., Hamon, M., Giros, B., Betancur, C. Neuroscience (2004) [Pubmed]
  8. Evidence for neurotensin as a non-adrenergic, non-cholinergic neurotransmitter in guinea pig ileum. Goedert, M., Hunter, J.C., Ninkovic, M. Nature (1984) [Pubmed]
  9. Hypothermia and intolerance to cold induced by intracisternal administration of the hypothalamic peptide neurotensin. Bissette, G., Nemeroff, C.B., Loosen, P.T., Prange, A.J., Lipton, M.A. Nature (1976) [Pubmed]
  10. Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice. Maoret, J.J., Anini, Y., Rouyer-Fessard, C., Gully, D., Laburthe, M. Int. J. Cancer (1999) [Pubmed]
  12. Endogenous neurotensin facilitates visceral nociception and is required for stress-induced antinociception in mice and rats. Gui, X., Carraway, R.E., Dobner, P.R. Neuroscience (2004) [Pubmed]
  13. The partial agonist properties of levocabastine in neurotensin-induced analgesia. Dubuc, I., Remande, S., Costentin, J. Eur. J. Pharmacol. (1999) [Pubmed]
  14. Cross-tolerance between ethanol and neurotensin in mice selectively bred for ethanol sensitivity. Erwin, V.G., Campbell, A.D., Myers, R., Womer, D.E. Pharmacol. Biochem. Behav. (1995) [Pubmed]
  15. Structure, functional expression, and cerebral localization of the levocabastine-sensitive neurotensin/neuromedin N receptor from mouse brain. Mazella, J., Botto, J.M., Guillemare, E., Coppola, T., Sarret, P., Vincent, J.P. J. Neurosci. (1996) [Pubmed]
  16. Desensitization of neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115. Gilbert, J.A., Strobel, T.R., Richelson, E. Biochem. Pharmacol. (1988) [Pubmed]
  17. Regulation of DARPP-32 Thr75 phosphorylation by neurotensin in neostriatal neurons: involvement of glutamate signalling. Matsuyama, S., Fukui, R., Higashi, H., Nishi, A. Eur. J. Neurosci. (2003) [Pubmed]
  18. The effects of deleting the mouse neurotensin receptor NTR1 on central and peripheral responses to neurotensin. Pettibone, D.J., Hess, J.F., Hey, P.J., Jacobson, M.A., Leviten, M., Lis, E.V., Mallorga, P.J., Pascarella, D.M., Snyder, M.A., Williams, J.B., Zeng, Z. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  19. Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin. Navarro, V., Martin, S., Sarret, P., Nielsen, M.S., Petersen, C.M., Vincent, J., Mazella, J. FEBS Lett. (2001) [Pubmed]
  20. Radiolabeled ligands specific for the G protein-coupled state of neurotensin receptors. Gaudriault, G., Zsürger, N., Vincent, J.P. J. Neurochem. (1996) [Pubmed]
  21. Anorexigenic hormones leptin, insulin, and alpha-melanocyte-stimulating hormone directly induce neurotensin (NT) gene expression in novel NT-expressing cell models. Cui, H., Cai, F., Belsham, D.D. J. Neurosci. (2005) [Pubmed]
  22. Amphetamine-elicited striatal Fos expression is attenuated in neurotensin null mutant mice. Fadel, J., Dobner, P.R., Deutch, A.Y. Neurosci. Lett. (2006) [Pubmed]
  23. Inhibition of neurotensin-induced pancreatic carcinoma growth by a nonpeptide neurotensin receptor antagonist, SR48692. Iwase, K., Evers, B.M., Hellmich, M.R., Kim, H.J., Higashide, S., Gully, D., Thompson, J.C., Townsend, C.M. Cancer (1997) [Pubmed]
  24. Regional and cellular distribution of low affinity neurotensin receptor mRNA in adult and developing mouse brain. Sarret, P., Beaudet, A., Vincent, J.P., Mazella, J. J. Comp. Neurol. (1998) [Pubmed]
  25. A single class of neurotensin receptors with high affinity in neuroblastoma X glioma NG108-15 hybrid cells that mediate facilitation of synaptic transmission. Nakagawa, Y., Higashida, H., Miki, N. J. Neurosci. (1984) [Pubmed]
  26. Identification of the receptor subtype involved in the analgesic effect of neurotensin. Dubuc, I., Sarret, P., Labbé-Jullié, C., Botto, J.M., Honoré, E., Bourdel, E., Martinez, J., Costentin, J., Vincent, J.P., Kitabgi, P., Mazella, J. J. Neurosci. (1999) [Pubmed]
  27. Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception. Maeno, H., Yamada, K., Santo-Yamada, Y., Aoki, K., Sun, Y.J., Sato, E., Fukushima, T., Ogura, H., Araki, T., Kamichi, S., Kimura, I., Yamano, M., Maeno-Hikichi, Y., Watase, K., Aoki, S., Kiyama, H., Wada, E., Wada, K. Brain Res. (2004) [Pubmed]
  28. Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line. Dicou, E., Vincent, J.P., Mazella, J. J. Neurosci. Res. (2004) [Pubmed]
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