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Neurotensin
Identifiers

CAS Number	39379-15-2^Y
3D model (JSmol)	Interactive image
ChemSpider	17290409^N
PubChem CID	16133836
InChI InChI=1S/C78H121N21O20/c1-7-43(6)63(73(115)96-57(76(118)119)37-42(4)5)97-70(112)55(39-45-21-25-47(101)26-22-45)95-72(114)59-18-13-35-99(59)75(117)52(16-11-33-86-78(83)84)90-64(106)48(15-10-32-85-77(81)82)89-71(113)58-17-12-34-98(58)74(116)51(14-8-9-31-79)91-69(111)56(40-60(80)102)94-66(108)50(28-30-62(104)105)88-68(110)54(38-44-19-23-46(100)24-20-44)93-67(109)53(36-41(2)3)92-65(107)49-27-29-61(103)87-49/h19-26,41-43,48-59,63,100-101H,7-18,27-40,79H2,1-6H3,(H2,80,102)(H,87,103)(H,88,110)(H,89,113)(H,90,106)(H,91,111)(H,92,107)(H,93,109)(H,94,108)(H,95,114)(H,96,115)(H,97,112)(H,104,105)(H,118,119)(H4,81,82,85)(H4,83,84,86)/t43-,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,63-/m0/s1^N Key: PCJGZPGTCUMMOT-ISULXFBGSA-N^N InChI=1/C78H121N21O20/c1-7-43(6)63(73(115)96-57(76(118)119)37-42(4)5)97-70(112)55(39-45-21-25-47(101)26-22-45)95-72(114)59-18-13-35-99(59)75(117)52(16-11-33-86-78(83)84)90-64(106)48(15-10-32-85-77(81)82)89-71(113)58-17-12-34-98(58)74(116)51(14-8-9-31-79)91-69(111)56(40-60(80)102)94-66(108)50(28-30-62(104)105)88-68(110)54(38-44-19-23-46(100)24-20-44)93-67(109)53(36-41(2)3)92-65(107)49-27-29-61(103)87-49/h19-26,41-43,48-59,63,100-101H,7-18,27-40,79H2,1-6H3,(H2,80,102)(H,87,103)(H,88,110)(H,89,113)(H,90,106)(H,91,111)(H,92,107)(H,93,109)(H,94,108)(H,95,114)(H,96,115)(H,97,112)(H,104,105)(H,118,119)(H4,81,82,85)(H4,83,84,86)/t43-,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,63-/m0/s1
SMILES CC[C@H](C)[C@@H](/C(=N/[C@@H](CC(C)C)C(=O)O)/O)/N=C(/[C@H](Cc1ccc(cc1)O)/N=C(/[C@@H]2CCCN2C(=O)[C@H](CCCNC(=N)N)/N=C(/[C@H](CCCNC(=N)N)/N=C(/[C@@H]3CCCN3C(=O)[C@H](CCCCN)/N=C(/[C@H](CC(=N)O)/N=C(/[C@H](CCC(=O)O)/N=C(/[C@H](Cc4ccc(cc4)O)/N=C(\[C@H](CC(C)C)/N=C(\[C@@H]5CCC(=N5)O)/O)/O)\O)\O)\O)\O)\O)\O)\O
Properties
Chemical formula	C₇₈H₁₂₁N₂₁O₂₀
Molar mass	1672.92
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is ^YN ?)
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.^[5]

Neurotensin is distributed throughout the central nervous system, with highest levels in the hypothalamus, amygdala and nucleus accumbens. It induces a variety of effects, including analgesia, hypothermia and increased locomotor activity. It is also involved in regulation of dopamine pathways. In the periphery, neurotensin is found in enteroendocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction.^[6]

Sequence and biosynthesis

Neurotensin shares significant sequence similarity in its 6 C-terminal amino acids with several other neuropeptides, including neuromedin N (which is derived from the same precursor). This C-terminal region is responsible for the full biological activity, the N-terminal portion having a modulatory role. The neurotensin/neuromedin N precursor can also be processed to produce large 125–138 amino acid peptides with the neurotensin or neuromedin N sequence at their C terminus. These large peptides appear to be less potent than their smaller counterparts, but are also less sensitive to degradation and may represent endogenous, long-lasting activators in a number of pathophysiological situations.

The sequence of bovine neurotensin was determined to be pyroGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH.^[7] Neurotensin is synthesized as part of a 169 or 170 amino acid precursor protein that also contains the related neuropeptide neuromedin N.^[8]^[9] 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

Neurotensin is a potent mitogen for colorectal cancer.^[10]

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.^[11] 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.^[12]

Neurotensin is an endogenous neuropeptide involved in thermoregulation that can induce hypothermia and neuroprotection in experimental models of cerebral ischemia.^[13]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000133636 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000019890 - Ensembl, May 2017
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ 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.
^ Friry C, Feliciangeli S, Richard F, Kitabgi P, Rovere C (February 2002). "Production of recombinant large proneurotensin/neuromedin N-derived peptides and characterization of their binding and biological activity". Biochem. Biophys. Res. Commun. 290 (4): 1161–8. doi:10.1006/bbrc.2001.6308. PMID 11811984.
^ 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 . 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 (September 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 . 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 . PMID 11427716.
^ Katz LM, Young A, Frank JE, Wang Y, Park K (March 2004). "Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia". Crit. Care Med. 32 (3): 806–10. doi:10.1097/01.CCM.0000114998.00860.FD. PMID 15090966.

External links

Neurotensin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

NMDAR2B tyrosine phosphorylation is involved in thermal nociception.

Delawary M, Tezuka T, Kiyama Y, Yokoyama K, Wada E, Wada K, Manabe T, Yamamoto T, Nakazawa T.SourceDivision of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Neuroscience letters.Neurosci Lett.2012 May 16;516(2):270-3. Epub 2012 Apr 10.
Previous studies found that the NMDA receptor-mediated signaling regulates thermal nociception, though the underlying molecular mechanism remains unclear. The GluN2B subunit of the NMDA receptor is tyrosine-phosphorylated, Tyr-1472 being the major phosphorylation site. In this study, we have found t
PMID 22516462

Corticotropin-releasing hormone and extracellular mitochondria augment IgE-stimulated human mast-cell vascular endothelial growth factor release, which is inhibited by luteolin.

Asadi S, Theoharides TC.AbstractABSTRACT:
Journal of neuroinflammation.J Neuroinflammation.2012 May 4;9(1):85. [Epub ahead of print]
ABSTRACT:BACKGROUND: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional social abilities, as well as learning deficits, and stereotypic behaviors. Many ASD patients have "allergic like" symptoms and respond disproportionally to stress.
PMID 22559745

Japanese Journal

ニューロテンシン (広範囲血液・尿化学検査免疫学的検査(第7版・4)その数値をどう読むか) -- (内分泌学的検査間脳下垂体関係(subunitを含む))

佐藤賢一,下瀬川徹
日本臨床 68(-) (982), 269-272, 2010-07-00
NAID 40017200738

Neurotensin promotes the dendrite elongation and the dendritic spine maturation of the cerebral cortex in vitro

GANDOU Chihiro,OHTANI Akiko,SENZAKI Kouji,SHIGA Takashi
Neuroscience research : the official journal of the Japan Neuroscience Society 66(3), 246-255, 2010-03-01
NAID 10027500829

P-001 同所性小腸移植ラット壁内神経系におけるNeurotensinの調節機構(ポスター移植1,Science and Art for Sick Children,第46回日本小児外科学会学術集会)

富田涼一,藤崎滋,朴英知,越永従道,草深竹志
日本小児外科学会雑誌 45(3), 523, 2009-05-20
NAID 110007383569

Related Pictures

★リンクテーブル★

リンク元	「ニューロテンシン」
拡張検索	「neurotensin receptor」「neurotensinoma」

「ニューロテンシン」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Neurotensin/neuromedin N precursor
Identifiers
Symbol	Pro-NT_NN
Pfam	PF07421
InterPro	IPR008055
OPM superfamily	294
OPM protein	2oyv
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

NTS
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2LNE, 2LNF, 2LNG, 2LYW, 3F6K, 2OYV, 2OYW, 4PO7
Identifiers
Aliases	NTS, NMN-125, NN, NT, NT/N, NTS1, neurotensin
External IDs	OMIM: 162650 MGI: 1328351 HomoloGene: 4506 GeneCards: NTS
Gene location (Human)
Chr.	Chromosome 12 (human)
End	85,882,992 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	102,490,486 bp
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• neuropeptide hormone activity; • protein binding;
Cellular component	• extracellular region; • transport vesicle; • cytoplasmic vesicle; • axon terminus;
Biological process	• signal transduction; • regulation of blood vessel size; • regulation of receptor activity; • G-protein coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	4922
	67405
	ENSG00000133636
	ENSMUSG00000019890
	P30990; Q6FH20
	Q9D3P9
	NM_006183
	NM_024435
	NP_006174; NP_006174.1
	NP_077755
	Wikidata
View/Edit Human	View/Edit Mouse