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NTS1 receptor

Family: Neurotensin receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 418 20q13-20q13 NTSR1 neurotensin receptor 1 (high affinity) 43-44,68
Mouse 7 424 2 H1-H4 Ntsr1 neurotensin receptor 1 43
Rat 7 424 3q43 Ntsr1 neurotensin receptor 1 66
Previous and Unofficial Names
Names References
NTRH 8
NTR1
NTSR1
Levocabastin-insensitive neurotensin receptor
High-affinity neurotensin receptor
NTR-1
NT1
NTR
LOC366274
Ntsr
Ntsr1_predicted
ntsr_predicted
NT-R-1
high-affinity levocabastine-insensitive neurotensin receptor
neurotensin receptor
neurotensin receptor (predicted)
neurotensin receptor 1
neurotensin receptor 1 (predicted)
neurotensin receptor type 1
NT-1R
Database Links
ChEMBL Target 12910 (Hs), 10485 (Mm), 17063 (Rn)
Ensembl ENSG00000101188 (Hs), ENSMUSG00000027568 (Mm), ENSRNOG00000028708 (Rn)
Entrez Gene 4923 (Hs), 18216 (Mm), 366274 (Rn)
GeneCards NTSR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Ntsr1 (Mm)
HomoloGene 68261 (Hs)
Human Protein Reference Database 01218 (Hs)
InterPro P30989 (Hs), O88319 (Mm), P20789 (Rn)
KEGG Gene hsa:4923 (Hs), mmu:18216 (Mm), rno:366274 (Rn)
OMIM 162651 (Hs)
PharmGKB Gene PA31821 (Hs)
PhosphoSitePlus P30989 (Hs), O88319 (Mm), P20789 (Rn)
Protein Ontology (PRO) PRO:000001627 (Hs)
RefSeq Nucleotide NM_002531 (Hs), NM_018766 (Mm), NM_001108967 (Rn)
RefSeq Protein NP_002522 (Hs), NP_061236 (Mm), NP_001102437 (Rn)
TreeFam ENSG00000101188 (Hs), ENSMUSG00000027568 (Mm), ENSRNOG00000028708 (Rn)
UniGene Hs. 110642 (Hs)
UniProt P30989 (Hs), O88319 (Mm), P20789 (Rn)
Wikipedia NTS1 receptor
Neurotensin receptors
Search for 3D structures on the PDB
Search by keyword: Neurotensin receptors NTS1 receptor Search by accession number: P20789, P30989, O88319
Natural/Endogenous Ligand(s)
large neuromedin N {Sp: Human} , large neuromedin N {Sp: Rat} , large neuromedin N {Sp: Mouse}
large neurotensin {Sp: Human}
neuromedin N {Sp: Human} , neuromedin N {Sp: Mouse, Rat}
neurotensin {Sp: Human, Mouse, Rat}
Comments: neurotensin is the most potent endogenous agonist
Rank order of potency (Human)
neurotensin > neuromedin N  [38]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]neurotensin (human, mouse, rat) Rn Full agonist 9.6 – 9.9 pKd 42,64
JMV449 Rn Full agonist 10.0 pKi 64
EISAI-2 Rn Full agonist 9.8 pKi 64
EISAI-1 Rn Full agonist 9.5 pKi 64
neurotensin {Sp: Human, Mouse, Rat} Rn Full agonist 8.2 – 10.0 pKi 22,41,64
neurotensin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 9.7 pKi 22,59
JMV458 Hs Full agonist 8.8 pKi 59
neuromedin N {Sp: Mouse, Rat} Rn Full agonist 8.7 pKi 64
JMV457 Hs Full agonist 5.8 pKi 59
JMV2004 Hs Full agonist 5.7 pKi 59
JMV431 Hs Full agonist 5.3 pKi 59
large neurotensin {Sp: Human} Hs Full agonist 8.7 pIC50 30
ABS-201 Mm Full agonist 8.0 pIC50 17
KH28 Hs Full agonist 7.92 pIC50 37
ABS212 Rn Full agonist 7.64 pIC50 40
Thr10contulakin-G Hs Full agonist 7.6 pIC50 20
large neuromedin N {Sp: Human} Hs Full agonist 7.4 pIC50 30
Thr10contulakin-G Rn Full agonist 7.1 pIC50 20
contulakin-G Rn Full agonist 6.3 pIC50 20
contulakin-G Hs Full agonist 6.0 pIC50 20
View species-specific agonist tables
Agonist Comments
The sequence of neurotensin is identical for all mammalian species.

Neurotensin and neuromedin N are synthesised from a common precursor [24].

Neurotensin and [125I]neurotensin bind with high affinity to NTS1 from all species 79-84.

[125I]-Trp11-neurotensin is specific for murine NTS1 receptors and exhibits low affinity for NTS1 receptors of human or other species [46,57].

[125I]-azidobenzoyl-neurotensin(2-13) is a photoreactive and radioactive analogue for covalent labelling of neurotensin receptors (including NTS1) from any species [15-16].

Xenopsin and contulakin-G are natural analogues of neurotensin from Xenopus laevis [5] and Conus geographus resepctively [20].

[α-bodipy]neurotensin(2-13) is a fluorescent synthetic analogue of neurotensin [7].

KH28, ABS212 and ABS-201 are able to cross the blood-brain barrier. ABS-201 and ABS212 are stable bioavailable NT analogues.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]SR48692 Rn Antagonist 8.5 pKd 42
SR48692 Hs Antagonist 8.4 pKi 59
SR48692 Rn Antagonist 8.0 – 8.6 pKi 41-42
SR48527 Rn Antagonist 7.1 – 7.5 pKi 42
SR142948A Hs Antagonist 8.9 pIC50 36
SR48692 Hs Antagonist 7.5 – 8.2 pIC50 36
View species-specific antagonist tables
Antagonist Comments
SR142948A binds to both NTS1 and NTS2 with similar nanomolar affinities.

SR48692 has a 10-30 times higher affinity for NTS1 than for NTS2 [35,42].

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  2-3,32,39,51,65,69
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family 		Adenylate cyclase stimulation
Adenylate cyclase inhibition
Guanylate cyclase stimulation
Other - See Comments
Comments:  Binding of neurotensin to the human NTS1 receptor indicates activation of MAP kinases and stimulates transcription of Krox-24, c-fos and Elk-1 [54,56].
References:  4,14,32-33,51,70
Tissue Distribution
Brain: cerebral cortex (cingulate and paraolfactory gyrus), basal gangla (caudate nucleus, putamen, nucleus accumbens), limbic system (basal and central amygdaloid nucleus) and brainstem (substantia nigra, ventral tegmental area).
Species:  Human
Technique:  Radioligand binding.
References:  62
Colon.
Species:  Human
Technique:  Radioligand binding.
References:  6
Endocrine pancreas
Species:  Mouse
Technique:  Immunohistochemistry
References:  19
Brain: basal forebrain, nucleus basalis, substantia nigra, substantia gelatinosa, ventral caudate-putamen, lateral reticular nucleus.
Species:  Rat
Technique:  Immunohistochemistry and Western blotting.
References:  29
Brain: islands of Calleja, diagonal band of Broca, magnocellular preoptic nucleus, presubiculum and parasubiculum, suprachiasmatic nucleus, anterodorsal nucleus of the thalamus, substantia nigra, ventral tegmental area, pontine nuclei and dorsal motor nucleus of the vagus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  11
Substantia nigra: pars compacta > pars reticula.
Species:  Rat
Technique:  immunocytochemistry.
References:  12
Substantia nigra pars compacta, ventral tegmental area.
Species:  Rat
Technique:  Radioligand binding.
References:  12
Spinal chord, dorsal root ganglia
Species:  Rat
Technique:  Immunohistochemistry
References:  61
Brain: diagonal band, medial septal nucleus, nucleus basalis magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia nigra and ventral tegmental area.
Species:  Rat
Technique:  in situ hybridisation.
References:  27
Brain: hypothalamus, epithalamus, ventral thalamus, septum, amygdala, pallidum.
Species:  Rat
Technique:  in situ hybridisation.
References:  1
Brain: olfactory bulb and tubercle, parts of the neocortex, lateral septum, diagonal band of Broca, caudate putamen, amygdala, dentate gyrus, anterior dorsal nucleus of the thalamus, suprachiasmatic nucleus of the hypothalamus, medial habenula, zona incerta, substantia nigra and ventral tegmental area.
Species:  Rat
Technique:  Radioligand binding.
References:  48
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of phosphatidyl inositol turnover in CHO cells transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  CHO cells stably expressing recombinant NTS1 receptors.
Response measured:  Stimulation of phosphoinositides hydrolysis.
References:  32,39,64,69
Measurement of Ca2+ levels in CHO cells transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of Ca2+ release from intracellular stores.
References:  31-32
Measurement of [35S]GTPγS incorporation in CHO cells transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of [35S]-GTPγS.
References:  32,38,50
Measurement of arachidonic acid release in CHO cells transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of arachidonic acid release.
References:  32,50
Measurement of MAP kinase activity in CHO cells transfected with the human NTS1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of MAP kinase activity.
References:  54
Measurement of chloride current in Xenopus oocytes transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  Xenopus oocytes.
Response measured:  Activation of Ca2+-dependent chloride current.
References:  8
Measurement of IPs accumulation in neonatal rat brain prisms endogenously expressing the NTS1 receptor.
Species:  Rat
Tissue:  Neonatal brain prisms.
Response measured:  Stimulation on IP accumulation.
References:  52
Measurement of Ca2+ and IP3 levels in human HL-60 cells endogenously expressing the NTS1 receptor.
Species:  Human
Tissue:  HL-60 cells.
Response measured:  Increase in Ca2+ and IP3 levels.
References:  18
Measurement of cAMP accumulation in CHO cells transfected with the rat NTS1 receptor.
Species:  Rat
Tissue:  CHO cells.
Response measured:  Stimulation of cAMP accumulation.
References:  64,70
Measurement of phosphatidyl inositol turnover in the human colonic adenocarcinoma cell line HT-29 endogenously expressing the NTS1 receptor.
Species:  Human
Tissue:  HL-29 cells.
Response measured:  Stimulation of phosphoinositides hydrolysis.
References:  2,51
Measurement of cGMP levels in mouse neuroblastoma N1E115 cells endogenously expressing the HTS1 receptor.
Species:  Mouse
Tissue:  Neuroblastoma N1E115 cells.
Response measured:  Increase in cGMP concentration.
References:  3-4,33,51,65
Measurement of Ca2+ levels and phosphatidyl inositol turnover in the cardiovascular system.
Species:  Human
Tissue:  Umbilical vein and aortic endothelial cells.
Response measured:  Stimulation of Ca2+ release and phosphatidyl inositol turnover.
References:  63
Physiological Functions
Modulation of turning behaviour.
Species:  Mouse
Tissue:  In vivo (brain).
References:  25
Stimulation of domamine efflux.
Species:  Mouse
Tissue:  In vivo (brain).
References:  45
Thermal regulation.
Species:  Mouse
Tissue:  In vivo.
References:  53,58
Regulation of feeding and weight control.
Species:  Mouse
Tissue:  In vivo.
References:  58
Regulation of locomotion.
Species:  Mouse
Tissue:  In vivo.
References:  58
Role in spacial learning.
Species:  Rat
Tissue:  In vivo.
References:  67
Interaction with the dopaminergic system.
Species:  Rat
Tissue:  In vivo.
References:  55
Smooth muscle contraction.
Species:  Human
Tissue:  Colonic smooth muscle strips.
References:  21
Smooth muscle contraction or relaxation.
Species:  Human
Tissue:  Segments of the duodenum or proximal colon.
References:  49
Analgesic effect (acute, tonic, neuropathic pain)
Species:  Rat
Tissue:  In vivo
References:  13,34,61
Analgesic effect
Species:  Mouse
Tissue:  In vivo
References:  47,60
Analgesic effect
Species:  Monkey
Tissue:  In vivo
References:  28
Thermoregulation modulator
Species:  Mouse
Tissue:  In vivo
References:  17
Physiological Consequences of Altering Gene Expression
NTS1 receptor knockout mice exhibit abolished neurotensin-induced dopamine efflux in the nucleus accumbens, as seen in wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  45
NTS1 receptor knockout mice have lost several responses to neurotensin, including central (hypothermia, hot-plate analgesia and motor ccordination) and gastrointestinal (colonic propulsion) effects.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  53
NTS1 receptor knockout mice exhibit hyperthermia, a small increase in body weight and an increase in food intake compared to the wild-type mice. They lack the hypolocomotive response to neurotensin seen in wild-type mice. There is no difference in neuotensin-induced analgesia between the knockout and wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  58
Rats overexpressing the NTS1 in the nucleus accumbens exhibit reduced dopaminergic transmission.
Species:  Rat
Tissue: 
Technique:  Retroviral infection.
References:  23
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ntsr1tm2Pang Ntsr1tm2Pang/Ntsr1tm2Pang
involves: 129P2/OlaHsd * C57BL/6J		 MGI:97386  MP:0001777 abnormal body temperature regulation PMID: 19223157 
Ntsr1tm1Fer Ntsr1tm1Fer/Ntsr1tm1Fer
Not Specified		 MGI:97386  MP:0001905 abnormal dopamine level PMID: 15030383 
Ntsr1tm1Pang Ntsr1tm1Pang/Ntsr1tm1Pang
C57BL/6-Ntsr1		 MGI:97386  MP:0003088 abnormal prepulse inhibition PMID: 19596359 
Ntsr1tm1Pang Ntsr1tm1Pang/Ntsr1tm1Pang
C57BL/6-Ntsr1		 MGI:97386  MP:0001486 abnormal startle reflex PMID: 19596359 
Ntsr1tm2Pang Ntsr1tm2Pang/Ntsr1tm2Pang
involves: 129P2/OlaHsd * C57BL/6J		 MGI:97386  MP:0002733 abnormal thermal nociception PMID: 19223157 
Ntsr1tm2Dgen Ntsr1tm2Dgen/Ntsr1tm2Dgen
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:97386  MP:0005534 decreased body temperature PMID: 11752130 
Ntsr1tm2Dgen Ntsr1tm2Dgen/Ntsr1tm2Dgen
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:97386  MP:0001982 decreased chemically-elicited antinociception PMID: 11752130 
Ntsr1tm1Pang Ntsr1tm1Pang/Ntsr1tm1Pang
C57BL/6-Ntsr1		 MGI:97386  MP:0001489 decreased startle reflex PMID: 19596359 
Ntsr1tm2Dgen Ntsr1tm2Dgen/Ntsr1tm2Dgen
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:97386  MP:0003290 hypoperistalsis PMID: 11752130 
Ntsr1+|Ntsr1tm2Dgen Ntsr1tm2Dgen/Ntsr1+
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:97386  MP:0003290 hypoperistalsis PMID: 11752130 
Ntsr1tm2Dgen Ntsr1tm2Dgen/Ntsr1tm2Dgen
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:97386  MP:0001405 impaired coordination PMID: 11752130 
Ntsr1tm1Fer Ntsr1tm1Fer/Ntsr1tm1Fer
C57BL/6		 MGI:97386  MP:0005533 increased body temperature PMID: 12384239 
Ntsr1tm1Fer Ntsr1tm1Fer/Ntsr1tm1Fer
C57BL/6		 MGI:97386  MP:0001260 increased body weight PMID: 12384239 
Ntsr1tm2Pang Ntsr1tm2Pang/Ntsr1tm2Pang
involves: 129P2/OlaHsd * C57BL/6J		 MGI:97386  MP:0002574 increased vertical activity PMID: 19223157 
Ntsr1tm1Fer Ntsr1tm1Fer/Ntsr1tm1Fer
C57BL/6		 MGI:97386  MP:0000008 increased white adipose tissue amount PMID: 12384239 
Ntsr1tm1Hmno Ntsr1tm1Hmno/Ntsr1tm1Hmno
B6.129P2-Ntsr1		 MGI:97386  MP:0002169 no abnormal phenotype detected PMID: 14725975 
Ntsr1tm1Dgen Ntsr1tm1Dgen/Ntsr1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:97386  MP:0002169 no abnormal phenotype detected
Ntsr1tm1Fer Ntsr1tm1Fer/Ntsr1tm1Fer
C57BL/6		 MGI:97386  MP:0001433 polyphagia PMID: 12384239 
Biologically Significant Variants
No splice variants of the NTS1 receptor have been found. There are two isoforms of the NTS1 receptor, corresponding to two translation initiation sites.
Type:  RNA editing.
Species:  Rat
References:  9-10
General Comments
A special issue of the journal "peptides" entitled "Neurotensin: Roles and Mechanisms" has recently been published [26].

REFERENCES

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1. Alexander, M. J. and Leeman, S. E. (1998) Widespread expression in adult rat forebrain of mRNA encoding high-affinity neurotensin receptor. J Comp Neurol, 402: 475-500. [PMID:9862322]

2. Amar, S., Kitabgi, P. and Vincent, J. P. (1986) Activation of phosphatidylinositol turnover by neurotensin receptors in the human colonic adenocarcinoma cell line HT29. FEBS Lett, 201: 31-36. [PMID:3011505]

3. Amar, S., Kitabgi, P. and Vincent, J. P. (1987) Stimulation of inositol phosphate production by neurotensin in neuroblastoma N1E115 cells: implication of GTP-binding proteins and relationship with the cyclic GMP response. J Neurochem, 49: 999-1006. [PMID:3040912]

4. Amar, S., Mazella, J., Checler, F., Kitabgi, P. and Vincent, J. P. (1985) Regulation of cyclic GMP levels by neurotensin in neuroblastoma clone N1E115. Biochem Biophys Res Commun, 129: 117-125. [PMID:2988544]

5. Araki, K., Tachibana, S., Uchiyama, M., Nakajima, T. and Yasuhara, T. (1975) Isolation and structure of a new active peptide xenopsin on rat stomach strip and some biogenic amines in the skin of Xenopus laevis. Chem Pharm Bull (Tokyo), 23: 3132-3140. [PMID:1218451]

6. Azriel, Y. and Burcher, E. (2001) Characterization and autoradiographic localization of neurotensin binding sites in human sigmoid colon. J Pharmacol Exp Ther, 297: 1074-1081. [PMID:11356931]

7. Beaudet, A., Nouel, D., Stroh, T., Vandenbulcke, F., Dal-Farra, C. and Vincent, J. P. (1998) Fluorescent ligands for studying neuropeptide receptors by confocal microscopy. Braz J Med Biol Res, 31: 1479-1489. [PMID:9921286]

8. Botto, J. M., Guillemare, E., Vincent, J. P. and Mazella, J. (1997) Effects of SR 48692 on neurotensin-induced calcium-activated chloride currents in the Xenopus oocyte expression system: agonist-like activity on the levocabastine-sensitive neurotensin receptor and absence of antagonist effect on the levocabastine insensitive neurotensin receptor. Neurosci Lett, 223: 193-196. [PMID:9080465]

9. Botto, J. M., Vincent, J. P. and Mazella, J. (1997) Existence of two translation initiation sites leading to the expression of two proteins from the rat high-affinity neurotensin-receptor cDNA: possible regulation by the 5' end non-coding region. Biochem J, 324: 389-393. [PMID:9182695]

10. Boudin, H., Lazaroff, B., Bachelet, C. M., Pélaprat, D., Rostene, W. and Beaudet, A. (2000) Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain. J Comp Neurol, 425: 45-57. [PMID:10940941]

11. Boudin, H., Pélaprat, D., Rostene, W. and Beaudet, A. (1996) Cellular distribution of neurotensin receptors in rat brain: immunohistochemical study using an antipeptide antibody against the cloned high affinity receptor. J Comp Neurol, 373: 76-89. [PMID:8876464]

12. Boudin, H., Pélaprat, D., Rostene, W., Pickel, V. M. and Beaudet, A. (1998) Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra. J Neurosci, 18: 8473-8484. [PMID:9763490]

13. Boules, M; Shaw, A; Liang, Y; Barbut, D; Richelson, E. (2009) NT69L, a novel analgesic, shows synergy with morphine. Brain Res., 1294: 22-8. [PMID:19651107]

14. Bozou, J. C., Amar, S., Vincent, J. P. and Kitabgi, P. (1986) Neurotensin-mediated inhibition of cyclic AMP formation in neuroblastoma N1E115 cells: involvement of the inhibitory GTP-binding component of adenylate cyclase. Mol Pharmacol, 29: 489-496. [PMID:3010077]

15. Chabry, J., Gaudriault, G., Vincent, J. P. and Mazella, J. (1993) Implication of various forms of neurotensin receptors in the mechanism of internalization of neurotensin in cerebral neurons. J Biol Chem, 268: 17138-17144. [PMID:8394329]

16. Chabry, J., Labbé-Jullié, C., Gully, D., Kitabgi, P., Vincent, J. P. and Mazella, J. (1994) Stable expression of the cloned rat brain neurotensin receptor into fibroblasts: binding properties, photoaffinity labeling, transduction mechanisms, and internalization. J Neurochem, 63: 19-27. [PMID:8207427]

17. Choi, KE; Hall, CL; Sun, JM; Wei, L; Mohamad, O; Dix, TA; Yu, SP. (2012) A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. FASEB J,  [Epub ahead of print]. [PMID:22459147]

18. Choi, S. Y., Chae, H. D., Park, T. J., Ha, H. and Kim, K. T. (1999) Characterization of high affinity neurotensin receptor NTR1 in HL-60 cells and its down regulation during granulocytic differentiation. Br J Pharmacol, 126: 1050-1056. [PMID:10193787]

19. Coppola, T; Béraud-Dufour, S; Antoine, A; Vincent, JP; Mazella, J. (2008) Neurotensin protects pancreatic beta cells from apoptosis. Int. J. Biochem. Cell Biol., 40 (10): 2296-302. [PMID:18456542]

20. Craig, A. G., Norberg, T., Griffin, D., Hoeger, C., Akhtar, M., Schmidt, K., Low, W., Dykert, J., Richelson, E., Navarro, V., Mazella, J., Watkins, M., Hillyard, D., Imperial, J., Cruz, L. J. and Olivera, B. M. (1999) Contulakin-G, an O-glycosylated invertebrate neurotensin. J Biol Chem, 274: 13752-13759. [PMID:10318778]

21. Croci, T., Aureggi, G., Guagnini, F., Manara, L., Gully, D., Fur, G. L., Maffrand, J. P., Mukenge, S., Ferla, G., Ferrara, P., Chalon, P. and Vita, N. (1999) In vitro functional evidence of different neurotensin-receptors modulating the motor response of human colonic muscle strips. Br J Pharmacol, 127: 1922-1928. [PMID:10482925]

22. Cusack, B., Jansen, K., McCormick, D. J., Chou, T., Pang, Y. and Richelson, E. (2000) A single amino acid of the human and rat neurotensin receptors (subtype 1) determining the pharmacological profile of a species-selective neurotensin agonist. Biochem Pharmacol, 60: 793-801. [PMID:10930533]

23. Cáceda, R., Kinkead, B., Owens, M. J. and Nemeroff, C. B. (2005) Virally mediated increased neurotensin 1 receptor in the nucleus accumbens decreases behavioral effects of mesolimbic system activation. J Neurosci, 25: 11748-11756. [PMID:16354933]

24. Dobner, P. R., Barber, D. L., Villa-Komaroff, L. and McKiernan, C. (1987) Cloning and sequence analysis of cDNA for the canine neurotensin/neuromedin N precursor. Proc Natl Acad Sci U S A, 84: 3516-3520. [PMID:3472221]

25. Dubuc, I., Sarret, P., Labbé-Jullié, C., Botto, J. M., Honore, E., Bourdel, E., Martinez, J., Costentin, J., Vincent, J. P., Kitabgi, P. and Mazella, J. (1999) Identification of the receptor subtype involved in the analgesic effect of neurotensin. J Neurosci, 19: 503-510. [PMID:9870978]

26. ed. Carraway, R.E., Pothoulakis, C. and Leeman, S. (2006) Neurotensin: Roles and Mechanisms. Peptides, 27: 2361-2534.

27. Elde, R., Schalling, M., Ceccatelli, S., Nakanishi, S. and Hökfelt, T. (1990) Localization of neuropeptide receptor mRNA in rat brain: initial observations using probes for neurotensin and substance P receptors. Neurosci Lett, 120: 134-138. [PMID:1705671]

28. Fantegrossi, WE; Ko, MC; Woods, JH; Richelson, E. (2005) Antinociceptive, hypothermic, hypotensive, and reinforcing effects of a novel neurotensin receptor agonist, NT69L, in rhesus monkeys. Pharmacol. Biochem. Behav., 80 (2): 341-9. [PMID:15680187]

29. Fassio, A., Evans, G., Grisshammer, R., Bolam, J. P., Mimmack, M. and Emson, P. C. (2000) Distribution of the neurotensin receptor NTS1 in the rat CNS studied using an amino-terminal directed antibody. Neuropharmacology, 39: 1430-1442. [PMID:10818259]

30. Friry, C., Feliciangeli, S., Richard, F., Kitabgi, P. and Rovere, C. (2002) Production of recombinant large proneurotensin/neuromedin N-derived peptides and characterization of their binding and biological activity. Biochem Biophys Res Commun, 290: 1161-1168. [PMID:11811984]

31. Gailly, P. (1998) Ca2+ entry in CHO cells, after Ca2+ stores depletion, is mediated by arachidonic acid. Cell Calcium, 24: 293-304. [PMID:9883283]

32. Gailly, P., Najimi, M. and Hermans, E. (2000) Evidence for the dual coupling of the rat neurotensin receptor with pertussis toxin-sensitive and insensitive G-proteins. FEBS Lett, 483: 109-113. [PMID:11042263]

33. Gilbert, J. A. and Richelson, E. (1984) Neurotensin stimulates formation of cyclic GMP in murine neuroblastoma clone N1E-115. Eur J Pharmacol, 99: 245-246. [PMID:6329783]

34. Guillemette, A; Dansereau, MA; Beaudet, N; Richelson, E; Sarret, P. (2012) Intrathecal administration of NTS1 agonists reverses nociceptive behaviors in a rat model of neuropathic pain. Eur J Pain, 16 (4): 473-84. [PMID:22396077]

35. Gully, D., Canton, M., Boigegrain, R., Jeanjean, F., Molimard, J. C., Poncelet, M., Gueudet, C., Heaulme, M., Leyris, R. and Brouard, A. (1993) Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci U S A, 90: 65-69. [PMID:8380498]

36. Gully, D., Labeeuw, B., Boigegrain, R., Oury-Donat, F., Bachy, A., Poncelet, M., Steinberg, R., Suaud-Chagny, M. F., Santucci, V., Vita, N., Pecceu, F., Labbé-Jullié, C., Kitabgi, P., Soubrie, P., Le Fur, G. and Maffrand, J. P. (1997) Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonist. J Pharmacol Exp Ther, 280: 802-812. [PMID:9023294]

37. Hadden, MK; Orwig, KS; Kokko, KP; Mazella, J; Dix, TA. (2005) Design, synthesis, and evaluation of the antipsychotic potential of orally bioavailable neurotensin (8-13) analogues containing non-natural arginine and lysine residues. Neuropharmacology, 49 (8): 1149-59. [PMID:16095636]

38. Hermans, E., Geurts, M. and Maloteaux, J. M. (1997) Agonist and antagonist modulation of [35S]-GTP gamma S binding in transfected CHO cells expressing the neurotensin receptor. Br J Pharmacol, 121: 1817-1823. [PMID:9283723]

39. Hermans, E., Maloteaux, J. M. and Octave, J. N. (1992) Phospholipase C activation by neurotensin and neuromedin N in Chinese hamster ovary cells expressing the rat neurotensin receptor. Brain Res Mol Brain Res, 15: 332-338. [PMID:1331689]

40. Hughes, FM; Shaner, BE; May, LA; Zotian, L; Brower, JO; Woods, RJ; Cash, M; Morrow, D; Massa, F; Mazella, J; et al.. (2010) Identification and functional characterization of a stable, centrally active derivative of the neurotensin (8-13) fragment as a potential first-in-class analgesic. J. Med. Chem., 53 (12): 4623-32. [PMID:20481538]

41. Labbé-Jullié, C., Barroso, S., Nicolas-Etève, D., Reversat, J. L., Botto, J. M., Mazella, J., Bernassau, J. M. and Kitabgi, P. (1998) Mutagenesis and modeling of the neurotensin receptor NTR1. Identification of residues that are critical for binding SR 48692, a nonpeptide neurotensin antagonist. J Biol Chem, 273: 16351-16357. [PMID:9632698]

42. Labbé-Jullié, C., Botto, J. M., Mas, M. V., Chabry, J., Mazella, J., Vincent, J. P., Gully, D., Maffrand, J. P. and Kitabgi, P. (1995) [3H]SR 48692, the first nonpeptide neurotensin antagonist radioligand: characterization of binding properties and evidence for distinct agonist and antagonist binding domains on the rat neurotensin receptor. Mol Pharmacol, 47: 1050-1056. [PMID:7746272]

43. Laurent, P., Clerc, P., Mattei, M. G., Forgez, P., Dumont, X., Ferrara, P., Caput, D. and Rostene, W. (1994) Chromosomal localization of mouse and human neurotensin receptor genes. Mamm Genome, 5: 303-306. [PMID:8075503]

44. Le, F., Groshan, K., Zeng, X. P. and Richelson, E. (1997) Characterization of the genomic structure, promoter region, and a tetranucleotide repeat polymorphism of the human neurotensin receptor gene. J Biol Chem, 272: 1315-1322. [PMID:8995438]

45. Leonetti, M., Brun, P., Clerget, M., Steinberg, R., Soubrie, P., Renaud, B. and Suaud-Chagny, M. F. (2004) Specific involvement of neurotensin type 1 receptor in the neurotensin-mediated in vivo dopamine efflux using knock-out mice. J Neurochem, 89: 1-6. [PMID:15030383]

46. Mazella, J., Poustis, C., Labbe, C., Checler, F., Kitabgi, P., Granier, C., van Rietschoten, J. and Vincent, J. P. (1983) Monoiodo-[Trp11]neurotensin, a highly radioactive ligand of neurotensin receptors. Preparation, biological activity, and binding properties to rat brain synaptic membranes. J Biol Chem, 258: 3476-3481. [PMID:6300046]

47. Mechanic, JA; Sutton, JE; Berson, AE; Wu, X; Kwan, J; Schreiber, R; Pang, Z; Button, DC. (2009) Involvement of the neurotensin receptor 1 in the behavioral effects of two neurotensin agonists, NT-2 and NT69L: lack of hypothermic, antinociceptive and antipsychotic actions in receptor knockout mice. Eur Neuropsychopharmacol, 19 (7): 466-75. [PMID:19223157]

48. Moyse, E., Rostene, W., Vial, M., Leonard, K., Mazella, J., Kitabgi, P., Vincent, J. P. and Beaudet, A. (1987) Distribution of neurotensin binding sites in rat brain: a light microscopic radioautographic study using monoiodo [125I]Tyr3-neurotensin. Neuroscience, 22: 525-536. [PMID:3313097]

49. Mulè, F., Serio, R., Postorino, A., Vetri, T. and Bonvissuto, F. (1996) Antagonism by SR 48692 of mechanical responses to neurotensin in rat intestine. Br J Pharmacol, 117: 488-492. [PMID:8821538]

50. Najimi, M., Gailly, P., Maloteaux, J. M. and Hermans, E. (2002) Distinct regions of C-terminus of the high affinity neurotensin receptor mediate the functional coupling with pertussis toxin sensitive and insensitive G-proteins. FEBS Lett, 512: 329-333. [PMID:11852105]

51. Oury-Donat, F., Thurneyssen, O., Gonalons, N., Forgez, P., Gully, D., Le Fur, G. and Soubrie, P. (1995) Characterization of the effect of SR48692 on inositol monophosphate, cyclic GMP and cyclic AMP responses linked to neurotensin receptor activation in neuronal and non-neuronal cells. Br J Pharmacol, 116: 1899-1905. [PMID:8528577]

52. Pereyra-Alfonso, S., López Ordieres, M. G., del V Armanino, M. and de Lores Arnaiz, G. R. (2005) High-affinity neurotensin receptor is involved in phosphoinositide hydrolysis stimulation by carbachol in neonatal rat brain. Brain Res Dev Brain Res, 154: 247-254. [PMID:15707678]

53. 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. and Zeng, Z. (2002) The effects of deleting the mouse neurotensin receptor NTR1 on central and peripheral responses to neurotensin. J Pharmacol Exp Ther, 300: 305-313. [PMID:11752130]

54. Poinot-Chazel, C., Portier, M., Bouaboula, M., Vita, N., Pecceu, F., Gully, D., Monroe, J. G., Maffrand, J. P., Le Fur, G. and Casellas, P. (1996) Activation of mitogen-activated protein kinase couples neurotensin receptor stimulation to induction of the primary response gene Krox-24. Biochem J, 320: 145-151. [PMID:8947479]

55. Poncelet, M., Souilhac, J., Gueudet, C., Terranova, J. P., Gully, D., Le Fur, G. and Soubrie, P. (1994) Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats. Psychopharmacology (Berl), 116: 237-241. [PMID:7862953]

56. Portier, M., Combes, T., Gully, D., Maffrand, J. P. and Casellas, P. (1998) Neurotensin type 1 receptor-mediated activation of krox24, c-fos and Elk-1: preventing effect of the neurotensin antagonists SR 48692 and SR 142948. FEBS Lett, 432: 88-93. [PMID:9710257]

57. Poustis, C., Mazella, J., Kitabgi, P. and Vincent, J. P. (1984) High-affinity neurotensin binding sites in differentiated neuroblastoma N1E115 cells. J Neurochem, 42: 1094-1100. [PMID:6699640]

58. Remaury, A., Vita, N., Gendreau, S., Jung, M., Arnone, M., Poncelet, M., Culouscou, J. M., Le Fur, G., Soubrie, P., Caput, D., Shire, D., Kopf, M. and Ferrara, P. (2002) Targeted inactivation of the neurotensin type 1 receptor reveals its role in body temperature control and feeding behavior but not in analgesia. Brain Res, 953: 63-72. [PMID:12384239]

59. Richard, F., Barroso, S., Martinez, J., Labbé-Jullié, C. and Kitabgi, P. (2001) Agonism, inverse agonism, and neutral antagonism at the constitutively active human neurotensin receptor 2. Mol Pharmacol, 60: 1392-1398. [PMID:11723247]

60. Roussy, G; Beaudry, H; Lafrance, M; Belleville, K; Beaudet, N; Wada, K; Gendron, L; Sarret, P. (2010) Altered morphine-induced analgesia in neurotensin type 1 receptor null mice. Neuroscience, 170 (4): 1286-94. [PMID:20727387]

61. Roussy, G; Dansereau, MA; Doré-Savard, L; Belleville, K; Beaudet, N; Richelson, E; Sarret, P. (2008) Spinal NTS1 receptors regulate nociceptive signaling in a rat formalin tonic pain model. J. Neurochem., 105 (4): 1100-14. [PMID:18182046]

62. Sarrieau, A., Javoy-Agid, F., Kitabgi, P., Dussaillant, M., Vial, M., Vincent, J. P., Agid, Y. and Rostène, W. H. (1985) Characterization and autoradiographic distribution of neurotensin binding sites in the human brain. Brain Res, 348: 375-380. [PMID:4075096]

63. Schaeffer, P., Laplace, M. C., Savi, P., Pflieger, A. M., Gully, D. and Herbert, J. M. (1995) Human umbilical vein endothelial cells express high affinity neurotensin receptors coupled to intracellular calcium release. J Biol Chem, 270: 3409-3413. [PMID:7852427]

64. Skrzydelski, D., Lhiaubet, A. M., Lebeau, A., Forgez, P., Yamada, M., Hermans, E., Rostene, W. and Pélaprat, D. (2003) Differential involvement of intracellular domains of the rat NTS1 neurotensin receptor in coupling to G proteins: a molecular basis for agonist-directed trafficking of receptor stimulus. Mol Pharmacol, 64: 421-429. [PMID:12869647]

65. Snider, R. M., Forray, C., Pfenning, M. and Richelson, E. (1986) Neurotensin stimulates inositol phospholipid metabolism and calcium mobilization in murine neuroblastoma clone N1E-115. J Neurochem, 47: 1214-1218. [PMID:3018165]

66. Tanaka, K., Masu, M. and Nakanishi, S. (1990) Structure and functional expression of the cloned rat neurotensin receptor. Neuron, 4: 847-854. [PMID:1694443]

67. Tirado-Santiago, G., Lázaro-Muñoz, G., Rodríguez-González, V. and Maldonado-Vlaar, C. S. (2006) Microinfusions of neurotensin antagonist SR 48692 within the nucleus accumbens core impair spatial learning in rats. Behav Neurosci, 120: 1093-1102. [PMID:17014260]

68. Vita, N., Laurent, P., Lefort, S., Chalon, P., Dumont, X., Kaghad, M., Gully, D., Le Fur, G., Ferrara, P. and Caput, D. (1993) Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor. FEBS Lett, 317: 139-142. [PMID:8381365]

69. Watson, M. A., Yamada, M., Yamada, M., Cusack, B., Veverka, K., Bolden-Watson, C. and Richelson, E. (1992) The rat neurotensin receptor expressed in Chinese hamster ovary cells mediates the release of inositol phosphates. J Neurochem, 59: 1967-1970. [PMID:1328536]

70. Yamada, M., Yamada, M., Watson, M. A. and Richelson, E. (1993) Neurotensin stimulates cyclic AMP formation in CHO-rNTR-10 cells expressing the cloned rat neurotensin receptor. Eur J Pharmacol, 244: 99-101. [PMID:8380559]

To cite this database page, please use the following:

Jean Mazella, Philippe Sarret, Jean-Pierre Vincent.
Neurotensin receptors: NTS1 receptor. Last modified on 15/02/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=309.


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