Neurotensin receptor 1

NTSR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LYW
Identifiers
Aliases	NTSR1, NTR, Neurotensin receptor 1, neurotensin receptor 1 (high affinity), NTR1
External IDs	OMIM: 162651; MGI: 97386; HomoloGene: 68261; GeneCards: NTSR1; OMA:NTSR1 - orthologs
Gene location (Human) Chr. Chromosome 20 (human) Band 20q13.33 Start 62,708,836 bp End 62,762,771 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 H4|2 103.04 cM Start 180,141,769 bp End 180,186,773 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle layer of sigmoid colon granulocyte substantia nigra prefrontal cortex monocyte transverse colon blood ganglionic eminence epithelium of colon cingulate gyrus Top expressed in barrel cortex substantia nigra ventral tegmental area embryo visual cortex zygote medullary collecting duct dorsomedial hypothalamic nucleus central gray substance of midbrain nucleus of stria terminalis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity protein homodimerization activity protein N-terminus binding signal transducer activity protein binding G protein-coupled neurotensin receptor activity identical protein binding protein heterodimerization activity Cellular component cytoplasm axon terminus integral component of membrane perikaryon Golgi apparatus membrane plasma membrane dendritic spine integral component of plasma membrane synapse dendritic shaft cell surface axon terminal bouton soma dendrite symmetric synapse endoplasmic reticulum mitochondrion neuron spine membrane raft cytoplasmic side of plasma membrane Biological process positive regulation of cation channel activity G protein-coupled receptor signaling pathway regulation of sensory perception of pain positive regulation of inositol phosphate biosynthetic process positive regulation of inhibitory postsynaptic potential adult locomotory behavior regulation of respiratory gaseous exchange negative regulation of apoptotic process positive regulation of release of sequestered calcium ion into cytosol D-aspartate import across plasma membrane learning inositol phosphate catabolic process regulation of membrane depolarization detection of temperature stimulus involved in sensory perception of pain response to lipid positive regulation of arachidonic acid secretion positive regulation of glutamate secretion positive regulation of apoptotic process negative regulation of release of sequestered calcium ion into cytosol positive regulation of gamma-aminobutyric acid secretion temperature homeostasis neuropeptide signaling pathway negative regulation of systemic arterial blood pressure signal transduction regulation of action potential chemical synaptic transmission L-glutamate import across plasma membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4923 18216 Ensembl ENSG00000101188 ENSMUSG00000027568 UniProt P30989 O88319 RefSeq (mRNA) NM_002531 NM_018766 RefSeq (protein) NP_002522 NP_061236 Location (UCSC) Chr 20: 62.71 – 62.76 Mb Chr 2: 180.14 – 180.19 Mb PubMed search
Wikidata
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Neurotensin receptor type 1 is a protein that in humans is encoded by the NTSR1 gene. The neurotensin receptor is primarily responsible for mediating the effects of the neuropeptide neurotensin.

Structure

Neurotensin receptor type 1 (NTSR1) is a member of the class A G protein-coupled receptor (GPCR) superfamily, characterized by its canonical structure of seven transmembrane α-helices connected by extracellular and intracellular loops. High-resolution crystal structures of NTSR1 have been determined in various functional states, including complexes with peptide agonists (such as the endogenous neurotensin fragment NTS8-13), non-peptide agonists, partial agonists, and antagonists, as well as in the ligand-free (apo) state.

The neurotensin binding pocket is located on the extracellular side of the receptor, where neurotensin binds in an extended conformation nearly perpendicular to the membrane, with the C-terminus oriented toward the receptor core. Key interactions involve charged residues in the binding pocket and the C-terminal arginine of neurotensin, while the receptor’s activation is associated with conformational changes that propagate from the ligand-binding site through the transmembrane helices to the intracellular side. The intracellular region of NTSR1 interacts with G proteins and β-arrestins, facilitating downstream signaling and receptor internalization; phosphorylation of specific intracellular sites is critical for stable β-arrestin binding. Notably, the receptor also contains an amphipathic helix 8 following transmembrane helix 7, although its stability and presence may vary among different receptor states and constructs.

Function

Neurotensin receptor 1, also called NTSR1, 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 and regulation of intestinal motility and secretion.

Neuromodulation

SBI-553 has demonstrated allosteric modulation potential via Beta-arrestin-2 signaling.

The anti-nociceptive properties of NTSR1 has been shown to be modulated by SBI-810, an analog of SBI-553 via inhibition of NMDA receptor activity as well as extracellular-regulated signal kinase signaling in spinal cord neurons. SBI-810 outperformed gabapentin and oliceridine in reducing opioid-induced reduced conditioned place preference, guarding, and facial grimacing in mice, indicating superior mitigation of opioid withdrawal.

Ligands

• ML314 – β-arrestin biased agonist
• Neurotensin (NT1)

See also

• Neurotensin receptor

Further reading

• Vincent JP (Oct 1995). "Neurotensin receptors: binding properties, transduction pathways, and structure". Cellular and Molecular Neurobiology. 15 (5): 501–512. doi:10.1007/BF02071313. PMC 11563118. PMID 8719037. S2CID 13335185.
• Vincent JP, Mazella J, Kitabgi P (Jul 1999). "Neurotensin and neurotensin receptors". Trends in Pharmacological Sciences. 20 (7): 302–309. doi:10.1016/S0165-6147(99)01357-7. PMID 10390649.
• Vita N, Laurent P, Lefort S, Chalon P, Dumont X, Kaghad M, et al. (Feb 1993). "Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor". FEBS Letters. 317 (1–2): 139–142. doi:10.1016/0014-5793(93)81509-X. PMID 8381365. S2CID 5929592.
• Le F, Groshan K, Zeng XP, Richelson E (Jan 1997). "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): 1315–1322. doi:10.1074/jbc.272.2.1315. PMID 8995438.
• Boudin H, Pélaprat D, Rostène W, Pickel VM, Beaudet A (Oct 1998). "Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra". The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 18 (20): 8473–8484. doi:10.1523/JNEUROSCI.18-20-08473.1998. PMC 6792847. PMID 9763490.
• Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, et al. (Oct 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". The Journal of Biological Chemistry. 274 (42): 30202–30208. doi:10.1074/jbc.274.42.30202. PMID 10514511.
• Wang L, Friess H, Zhu Z, Graber H, Zimmermann A, Korc M, et al. (Feb 2000). "Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease". Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 6 (2): 566–571. PMID 10690540.
• Cusack B, Jansen K, McCormick DJ, Chou T, Pang Y, Richelson E (Sep 2000). "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. doi:10.1016/S0006-2952(00)00409-3. PMID 10930533.
• Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG (Jun 2001). "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): 19452–19460. doi:10.1074/jbc.M101450200. PMID 11279203.
• Leplatois P, Josse A, Guillemot M, Febvre M, Vita N, Ferrara P, et al. (Sep 2001). "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): 4860–4867. doi:10.1046/j.0014-2956.2001.02407.x. PMID 11559354.
• Lundquist JT, Büllesbach EE, Golden PL, Dix TA (Feb 2002). "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 : Official Journal of the American Peptide Society. 59 (2): 55–61. doi:10.1046/j.1397-002x.2001.10946.x. PMID 11906607.
• Somaï S, Gompel A, Rostène W, Forgez P (Jul 2002). "Neurotensin counteracts apoptosis in breast cancer cells". Biochemical and Biophysical Research Communications. 295 (2): 482–488. doi:10.1016/S0006-291X(02)00703-9. PMID 12150975.
• Martin S, Navarro V, Vincent JP, Mazella J (Oct 2002). "Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line". Gastroenterology. 123 (4): 1135–1143. doi:10.1053/gast.2002.36000. PMID 12360476.
• Toy-Miou-Leong M, Cortes CL, Beaudet A, Rostène W, Forgez P (Mar 2004). "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): 12636–12646. doi:10.1074/jbc.M303384200. PMID 14699144.
• Magazin M, Poszepczynska-Guigné E, Bagot M, Boumsell L, Pruvost C, Chalon P, et al. (Jan 2004). "Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor". The Journal of Investigative Dermatology. 122 (1): 111–118. doi:10.1046/j.0022-202X.2003.22131.x. PMID 14962098.
• Brun P, Mastrotto C, Beggiao E, Stefani A, Barzon L, Sturniolo GC, et al. (Apr 2005). "Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation". American Journal of Physiology. Gastrointestinal and Liver Physiology. 288 (4): G621 – G629. doi:10.1152/ajpgi.00140.2004. PMID 15764810.

External links

• "Neurotensin Receptors: NTS₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2012-04-02. Retrieved 2008-12-05.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.