Neurotensin receptor 1 explained

Neurotensin receptor type 1 is a protein that in humans is encoded by the NTSR1 gene.^{[1] [2]} For a crystal structure of NTS1, see pdb code 4GRV. In addition, high-resolution crystal structures have been determined in complex with the peptide full agonist NTS8-13, the non-peptide full agonist SRI-9829, the partial agonist RTI-3a, and the antagonists / inverse agonists SR48692 and SR142948A, as well as in the ligand-free apo state.,^[3] see PDB codes 6YVR (NTSR1-H4X:NTS8–13), 6Z4V (NTSR1-H4bmX:NTS8–13), 6Z8N (NTSR1-H4X:SRI-9829), 6ZA8 (NTSR1-H4X:RTI-3a), 6Z4S (NTSR1-H4bmX:SR48692), 6ZIN (NTSR1-H4X:SR48692), 6Z4Q (NTSR1-H4X: SR142948A), and 6Z66 (apo NTSR1-H4X).

Function

Neurotensin receptor 1, also called NTR1, belongs to the large superfamily of G-protein coupled receptors and is considered a class-A GPCR. NTSR1 mediates multiple biological processes through modulation by neurotensin, such as low blood pressure, high blood sugar, low body temperature, antinociception, anti-neuronal damage ^[4] and regulation of intestinal motility and secretion.^[2]

Ligands

• ML314 – β-arrestin biased agonist^[5]
• Neurotensin (NT1)

See also

• Neurotensin receptor

Further reading

• Vincent JP . Neurotensin receptors: binding properties, transduction pathways, and structure . Cellular and Molecular Neurobiology . 15 . 5 . 501–12 . Oct 1995 . 8719037 . 10.1007/BF02071313 . 13335185 .
• Vincent JP, Mazella J, Kitabgi P . Neurotensin and neurotensin receptors . Trends in Pharmacological Sciences . 20 . 7 . 302–9 . Jul 1999 . 10390649 . 10.1016/S0165-6147(99)01357-7 .
• Vita N, Laurent P, Lefort S, Chalon P, Dumont X, Kaghad M, Gully D, Le Fur G, Ferrara P, Caput D . Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor . FEBS Letters . 317 . 1–2 . 139–42 . Feb 1993 . 8381365 . 10.1016/0014-5793(93)81509-X . 5929592 . free .
• Le F, Groshan K, Zeng XP, Richelson E . Characterization of the genomic structure, promoter region, and a tetranucleotide repeat polymorphism of the human neurotensin receptor gene . The Journal of Biological Chemistry . 272 . 2 . 1315–22 . Jan 1997 . 8995438 . 10.1074/jbc.272.2.1315 . free .
• Boudin H, Pélaprat D, Rostène W, Pickel VM, Beaudet A . Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra . The Journal of Neuroscience . 18 . 20 . 8473–84 . Oct 1998 . 9763490 . 10.1523/JNEUROSCI.18-20-08473.1998. 6792847 . free .
• Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE . TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction . The Journal of Biological Chemistry . 274 . 42 . 30202–8 . Oct 1999 . 10514511 . 10.1074/jbc.274.42.30202 . free .
• Wang L, Friess H, Zhu Z, Graber H, Zimmermann A, Korc M, Reubi JC, Büchler MW . Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease . Clinical Cancer Research . 6 . 2 . 566–71 . Feb 2000 . 10690540 .
• Cusack B, Jansen K, McCormick DJ, Chou T, Pang Y, Richelson E . A single amino acid of the human and rat neurotensin receptors (subtype 1) determining the pharmacological profile of a species-selective neurotensin agonist . Biochemical Pharmacology . 60 . 6 . 793–801 . Sep 2000 . 10930533 . 10.1016/S0006-2952(00)00409-3 .
• Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG . Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis* . The Journal of Biological Chemistry . 276 . 22 . 19452–60 . Jun 2001 . 11279203 . 10.1074/jbc.M101450200 . free .
• Leplatois P, Josse A, Guillemot M, Febvre M, Vita N, Ferrara P, Loison G . Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor . European Journal of Biochemistry . 268 . 18 . 4860–7 . Sep 2001 . 11559354 . 10.1046/j.0014-2956.2001.02407.x . free .
• Lundquist JT, Büllesbach EE, Golden PL, Dix TA . Topography of the neurotensin (NT)(8-9) binding site of human NT receptor-1 probed with NT(8-13) analogs . The Journal of Peptide Research . 59 . 2 . 55–61 . Feb 2002 . 11906607 . 10.1046/j.1397-002x.2001.10946.x .
• Somaï S, Gompel A, Rostène W, Forgez P . Neurotensin counteracts apoptosis in breast cancer cells . Biochemical and Biophysical Research Communications . 295 . 2 . 482–8 . Jul 2002 . 12150975 . 10.1016/S0006-291X(02)00703-9 .
• Martin S, Navarro V, Vincent JP, Mazella J . Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line . Gastroenterology . 123 . 4 . 1135–43 . Oct 2002 . 12360476 . 10.1053/gast.2002.36000 . free .
• Toy-Miou-Leong M, Cortes CL, Beaudet A, Rostène W, Forgez P . Receptor trafficking via the perinuclear recycling compartment accompanied by cell division is necessary for permanent neurotensin cell sensitization and leads to chronic mitogen-activated protein kinase activation . The Journal of Biological Chemistry . 279 . 13 . 12636–46 . Mar 2004 . 14699144 . 10.1074/jbc.M303384200 . free .
• Magazin M, Poszepczynska-Guigné E, Bagot M, Boumsell L, Pruvost C, Chalon P, Culouscou JM, Ferrara P, Bensussan A . Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor . The Journal of Investigative Dermatology . 122 . 1 . 111–8 . Jan 2004 . 14962098 . 10.1046/j.0022-202X.2003.22131.x . free .
• Brun P, Mastrotto C, Beggiao E, Stefani A, Barzon L, Sturniolo GC, Palù G, Castagliuolo I . Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation . American Journal of Physiology. Gastrointestinal and Liver Physiology . 288 . 4 . G621–9 . Apr 2005 . 15764810 . 10.1152/ajpgi.00140.2004 .

External links

• Web site: Neurotensin Receptors: NTS₁ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-05 . 2012-04-02 . https://web.archive.org/web/20120402212312/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3004 . dead .

Notes and References

1. Laurent P, Clerc P, Mattei MG, Forgez P, Dumont X, Ferrara P, Caput D, Rostene W . Chromosomal localization of mouse and human neurotensin receptor genes . Mammalian Genome . 5 . 5 . 303–6 . May 1994 . 8075503 . 10.1007/BF00389545 . 30418560 . free .
2. Web site: Entrez Gene: NTSR1 neurotensin receptor 1 (high affinity).
3. Deluigi M, Klipp A, Klenk C, Merklinger L, Eberle SA, Morstein L, Heine P, Mittl PR, Ernst P, Kamenecka TM, He Y, Vacca S, Egloff P, Honegger A, Plückthun A . Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism . Science Advances . 7 . 5 . eabe5504 . January 2021 . 7840143 . 10.1126/sciadv.abe5504 . 33571132 . 2021SciA....7.5504D .
4. Liu Q, Hazan A, Grinman E, Angulo JA. 3 . Pharmacological activation of the neurotensin receptor 1 abrogates the methamphetamine-induced striatal apoptosis in the mouse brain. Brain Research. 1659 . 148–155. 2017 . 10.1016/j.brainres.2017.01.029. 28130052 . 6405660 .
5. Peddibhotla S, Hedrick MP, Hershberger P, et al. . Discovery of ML314, a Brain Penetrant Non-Peptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor . ACS Med Chem Lett . 4 . 9 . 846–851 . 2013 . 24611085 . 3940307 . 10.1021/ml400176n .