Neurotensin
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| Neurotensin | |||||||||||||
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| Symbols | NTS; NT; NMN-125; NN; NT/N; NTS1 | ||||||||||||
| External IDs | OMIM: 162650 MGI: 1328351 HomoloGene: 4506 GeneCards: NTS Gene | ||||||||||||
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| Species | Human | Mouse | |||||||||||
| Entrez | 4922 | 67405 | |||||||||||
| Ensembl | ENSG00000133636 | ENSMUSG00000019890 | |||||||||||
| UniProt | P30990 | Q9D3P9 | |||||||||||
| RefSeq (mRNA) | NM_006183 | NM_024435 | |||||||||||
| RefSeq (protein) | NP_006174 | NP_077755 | |||||||||||
| Location (UCSC) | Chr 12: 84.79 - 84.8 Mb | Chr 10: 101.91 - 101.92 Mb | |||||||||||
| PubMed search | [1] | [2] | |||||||||||
| Neurotensin | |
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| File:Neurotensin.png | |
| style="background: #F8EABA; text-align: center;" colspan="2" | Identifiers | |
| CAS number | 55508-42-4 |
| PubChem | 16129680 |
| style="background: #F8EABA; text-align: center;" colspan="2" | Properties | |
| Molecular formula | C78H121N21O20 |
| Molar mass | 1672.92 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) | |
| Infobox references | |
Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats.[1]
Structure
The sequence of bovine neurotensin was determined to be pyroGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH.[2] Neurotensin is synthesized as part of a 169-170 amino acid precursor protein that also contains the related neuropeptide neuromedin N.[3][4] The peptide coding domains are located in tandem near the carboxyl terminal end of the precursor and are bounded and separated by paired basic amino acid (lysine-arginine) processing sites.
Clinical significance
It has been associated with colorectal cancer.[5]
Neurotensin has been implicated in the modulation of dopamine signaling, and produces a spectrum of pharmacological effects resembling those of antipsychotic drugs, leading to the suggestion that neurotensin may be an endogenous neuroleptic. Neurotensin-deficient mice display defects in responses to several antipsychotic drugs consistent with the idea that neurotensin signaling is a key component underlying at least some antipsychotic drug actions [6] . These mice exhibit modest defects in prepulse inhibition (PPI) of the startle reflex, a model that has been widely used to investigate antipsychotic drug action in animals. Antipsychotic drug administration augments PPI under certain conditions. Comparisons between normal and neurotensin-deficient mice revealed striking differences in the ability of different antipsychotic drugs to augment PPI. While the atypical antipsychotic drug clozapine augmented PPI normally in neurotensin-deficient mice, the conventional antipsychotic haloperidol and the newer atypical antipsychotic quetiapine were ineffective in these mice, in contrast to normal mice where these drugs significantly augmented PPI. These results suggest that certain antipsychotic drugs require neurotensin for at least some of their effects. Neurotensin-deficient mice also display defects in striatal activation following haloperidol, but not clozapine administration in comparison to normal wild type mice, indicating that striatal neurotensin is required for the full spectrum of neuronal responses to a subset of antipsychotic drugs [7].
See also
References
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de:Neurotensin pl:Neurotensyna- ↑ Carraway R, Leeman SE (1973). "The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami". J. Biol. Chem. 248 (19): 6854–61. PMID 4745447.
- ↑ Carraway R, Leeman SE (1975). "The amino acid sequence of a hypothalamic peptide, neurotensin". J. Biol. Chem. 250 (5): 1907–11. PMID 1167549.
- ↑ Dobner PR, Barber DL, Villa-Komaroff L, McKiernan C (1987). "Cloning and sequence analysis of cDNA for the canine neurotensin/neuromedin N precursor". Proc. Natl. Acad. Sci. U.S.A. 84 (10): 3516–20. doi:10.1073/pnas.84.10.3516. PMC 304902 Freely accessible. PMID 3472221.
- ↑ Kislauskis E, Bullock B, McNeil S, Dobner PR (1988). "The rat gene encoding neurotensin and neuromedin N. Structure, tissue-specific expression, and evolution of exon sequences". J. Biol. Chem. 263 (10): 4963–8. PMID 2832414.
- ↑ Wang X, Wang Q, Ives KL, Evers BM (2006). "Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells". Clin. Cancer Res. 12 (18): 5346–55. doi:10.1158/1078-0432.CCR-06-0968. PMC 2613866 Freely accessible. PMID 17000667.
- ↑ Kinkead, B, Dobner PR, Egnatashvili, V, Murray, T, Deitemeyer, N, Nemeroff, CB (2005). "Neurotensin-deficient mice have deficits in prepulse inhibition: restoration by clozapine but no haloperidol, olanzapine, or quetiapine". J. Pharmacol. Exp. Ther. 315 (1): 256–264. doi:10.1124/jpet.105.087437. PMID 15987829.
- ↑ Dobner, PR, Fadel, J, Deitemeyer, N, Carraway, RE, Deutch, AY (2001). "Neurotensin-deficient mice show altered responses to antipsychotic drugs". Proc. Natl. Acad. Sci. USA. 98 (14): 8048–8053. doi:10.1073/pnas.141042198. PMC 35465 Freely accessible. PMID 11427716.
