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Link to original content: http://omim.org/entry/162650
HGNC Approved Gene Symbol: NTS
Cytogenetic location: 12q21.31 Genomic coordinates (GRCh38) : 12:85,874,295-85,882,992 (from NCBI)
Neurotensin is a tridecapeptide that is widely distributed throughout the central nervous system (Mai et al., 1987). Gerhard et al. (1989) found that in the CNS, neurotensin is localized to the catecholamine-containing neurons. A catecholamine-producing cell line can also produce NTS. Lithium salts, widely used in the treatment of manic-depressive patients, dramatically potentiate NTS gene expression in this cell line.
Using canine NTS to probe a human brain genomic library, Bean et al. (1992) obtained a partial cDNA, lacking exon 4, encoding NTS. The 120-amino acid fragment was predicted to be 89% identical to dog and cow sequences. Comparison of the proximal 5-prime flanking sequences of the human and rat genes revealed striking conservation of the cis regulatory sequences. In situ hybridization analysis identified NTS expression in approximately 10% of ventral mesencephalon cells of control as well as schizophrenic subjects.
Dong et al. (1998) obtained the remaining sequence for the full-length cDNA encoding NTS. The predicted 170-amino acid protein is 78% identical to the rat sequence. The authors observed high expression of NTS in Hep3B but not in HepG2 hepatoma cell lines. Low expression appeared to be mediated in part by DNA methylation.
Using RT-PCR, immunofluorescence microscopy, and flow cytometric analysis, Saada et al. (2012) detected expression of NTS, NTSR1, NTSR2 (605538), and NTSR3 (SORT1; 602458) in primary human B lymphocytes and human B-cell lines at different stages of maturation. NTS exerted a proliferative and antiapoptotic effect on B cells. Patients with chronic B-cell lymphocytic leukemia (CLL; 151400) showed no expression of NTS and increased expression of NTSR2. Saada et al. (2012) concluded that NTS and its 2 specific receptors, NTSR1 and NTSR2, are expressed in human B lymphocytes, as previously found for T cells, macrophages, and dendritic cells, indicating that NTS may modulate immune responses and cell interactions.
Gerhard et al. (1989) used a canine cDNA as a probe on a somatic cell hybrid panel to determine that the human NTS gene is located on chromosome 12. Marondel et al. (1996) used YAC screening and fluorescence in situ hybridization to map the NTS gene to chromosome 12q21 between markers D12S1444 and D12S81.
Donelan et al. (2006) used intradermal injection of various peptides to assess vascular permeability, as measured by Evans blue extravasation, in rat skin. They found that corticotropin-releasing hormone (CRH; 122560) and Nts potently induced vascular permeability. The effect of Crh and Nts was blocked by a neurotensin receptor antagonist and did not occur in Nts -/- mice. RT-PCR analysis showed that Crh and Nts were present in dorsal root ganglia and that Crh receptor (CRHR1; 122561) was expressed on mouse skin mast cells. Donelan et al. (2006) concluded that NTS is involved in the action of CRH. They suggested that mast cell-neuron interactions and mast cell activation may be involved in the pathophysiology of skin conditions such as atopic dermatitis, urticaria, and psoriasis.
Piliponsky et al. (2008) found that intraperitoneal and plasma concentrations of neurotensin are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacologic antagonist of neurotensin, or neurotensin-deficient mice, showed reduced mortality during severe CLP. In mice, mast cells can degrade neurotensin and reduce neurotensin-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor-1 and neurolysin (611530). Piliponsky et al. (2008) concluded that neurotensin contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower neurotensin concentrations, and suggested that mast cell-dependent reduction in neurotensin levels contributes to the ability of mast cells to enhance survival after CLP.
Li et al. (2016) showed that neurotensin-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis, and insulin resistance associated with high fat consumption. Li et al. (2016) further demonstrated that neurotensin attenuates the activation of AMPK and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving neurotensin receptors NTR1 (NTSR1; 162651) and NTR3 (NTSR3; 602458). Consistent with the findings in mice, expression of neurotensin in Drosophila midgut enteroendocrine cells resulted in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells), and decreased AMPK activation. In humans, Li et al. (2016) showed that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-neurotensin, and in longitudinal studies among nonobese subjects, high levels of pro-neurotensin denote a doubling of the risk of developing obesity later in life. increased fat absorption and obesity.
Bean, A. J., Dagerlind, A., Hokfelt, T., Dobner P. R. Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls. Neuroscience 50: 259-268, 1992. [PubMed: 1436492] [Full Text: https://doi.org/10.1016/0306-4522(92)90421-w]
Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T. C. Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Proc. Nat. Acad. Sci. 103: 7759-7764, 2006. [PubMed: 16682628] [Full Text: https://doi.org/10.1073/pnas.0602210103]
Dong, Z., Wang, X., Zhao, Q., Townsend, C. M., Jr., Evers, B. M. DNA methylation contributes to expression of the human neurotensin/neuromedin N gene. Am. J. Physiol. 274: G535-G543, 1998. [PubMed: 9530155] [Full Text: https://doi.org/10.1152/ajpgi.1998.274.3.G535]
Gerhard, D. S., Dobner, P. R., Bruns, G. A. P. Localization of the neurotensin gene to human chromosome 12. (Abstract) Cytogenet. Cell Genet. 51: 1003 only, 1989.
Li, J., Song, J., Zaytseva, Y. Y., Liu, Y., Rychahou, P., Jiang, K., Starr, M. E., Kim, J. T., Harris, J. W., Yiannikouris, F. B., Katz, W. S., Nilsson, P. M., Orho-Melander, M., and 13 others. An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature 533: 411-415, 2016. [PubMed: 27193687] [Full Text: https://doi.org/10.1038/nature17662]
Mai, J. K., Triepel, J., Metz, J. Neurotensin in human brain. Neuroscience 22: 499-524, 1987. [PubMed: 3670596] [Full Text: https://doi.org/10.1016/0306-4522(87)90349-6]
Marondel, I, Renault, B., Lieman, J., Ward, D., Kucherlapati, R. Physical mapping of the human neurotensin gene (NTS) between markers D12S1444 and D12S81 on chromosome 12q21. Genomics 38: 243-245, 1996. [PubMed: 8954810] [Full Text: https://doi.org/10.1006/geno.1996.0624]
Piliponsky, A. M., Chen, C.-C., Nishimura, T., Metz, M., Rios, E. J., Dobner, P. R., Wada, E., Wada, K., Zacharias, S., Mohanasundaram, U. M., Faix, J. D., Abrink, M., Pejler, G., Pearl, R. G., Tsai, M., Galli, S. J. Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis. Nature Med. 14: 392-398, 2008. [PubMed: 18376408] [Full Text: https://doi.org/10.1038/nm1738]
Saada, S., Marget, P., Fauchais, A.-L., Lise, M.-C., Chemin, G., Sindou, P., Martel, C., Delpy, L., Vidal, E., Jaccard, A., Troutaud, D., Lalloue, F., Jauberteau, M.-O. Differential expression of neurotensin and specific receptors, NTSR1 and NTSR2, in normal and malignant human B lymphocytes. J. Immun. 189: 5293-5303, 2012. [PubMed: 23109725] [Full Text: https://doi.org/10.4049/jimmunol.1102937]