Neurotensin receptor explained
| neurotensin receptor 1 (high affinity) |
| Hgncid: | 8039 |
| Symbol: | NTSR1 |
| Altsymbols: | NTR |
| Entrezgene: | 4923 |
| Omim: | 162651 |
| Refseq: | NM_002531 |
| Uniprot: | P30989 |
| Chromosome: | 20 |
| Arm: | q |
| Band: | 13 |
| Locussupplementarydata: | -20q13 |
| neurotensin receptor 2 |
| Hgncid: | 8040 |
| Symbol: | NTSR2 |
| Altsymbols: | NTR2 |
| Entrezgene: | 23620 |
| Omim: | 605538 |
| Refseq: | NM_012344 |
| Uniprot: | O95665 |
| Chromosome: | 2 |
| Arm: | p |
| Band: | 25.1 |
| sortilin 1 |
| Hgncid: | 11186 |
| Symbol: | SORT1 |
| Altsymbols: | Gp95, NT3 |
| Entrezgene: | 6272 |
| Omim: | 602458 |
| Refseq: | NM_002959 |
| Uniprot: | Q99523 |
| Chromosome: | 1 |
| Arm: | p |
| Band: | 21.3 |
| Locussupplementarydata: | -1p13.1 |
Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin.[1] [2] Two of the receptors encoded by the and genes contain seven transmembrane helices and are G protein coupled. Numerous crystal structures have been reported for the neurotensin receptor 1 (NTS1).[3] The third receptor has a single transmembrane domain and is encoded by the gene.
Ligands
Agonists
- Peptide
- Beta-lactotensin (NTS2)[4]
- JMV-449
- Neurotensin
- Neuromedin N (NTS1 selective)
- PD-149,163 (NTS1 selective, reduced amide bond 8-13 fragment of neurotensin)
- Non-peptide
- NTS1 full agonist SRI-9829 [3]
- Partial agonists derived from SR-48692[5]
Antagonists
Biophysical Investigation
Unusually for GPCRs, NTS1 can be expressed in an active form in the bacteria E. coli.[8] It can be purified and analysed in vitro and has been analysed by a number of biophysical techniques such as surface plasmon resonance,[9] FRET[10] and cryo-electron microscopy.[11] Furthermore, high-resolution crystal structures of NTS1 have been determined in complex with the peptide full agonist NT8-13, the non-peptide full agonist SRI-9829, the partial agonist RTI-3a, and the antagonists / inverse agonists SR-48692 and SR-142948, as well as in the ligand-free apo state [3]
External links
- Web site: Neurotensin Receptors . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-04-24 . 2016-03-03 . https://web.archive.org/web/20160303210516/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1342 . dead .
Notes and References
- Vincent JP, Mazella J, Kitabgi P . Neurotensin and neurotensin receptors . Trends Pharmacol. Sci. . 20 . 7 . 302–309 . 1999 . 10390649 . 10.1016/S0165-6147(99)01357-7 .
- Pelaprat D . Interactions between neurotensin receptors and G proteins . Peptides . 27 . 10 . 2476–2487 . 2006 . 16919370 . 10.1016/j.peptides.2006.04.027 . 21730838 .
- 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 .
- Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M . Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist . Bioscience, Biotechnology, and Biochemistry . 67 . 4 . 940–3 . April 2003 . 12784648 . 10.1271/bbb.67.940. 83609327 . free .
- Thomas JB, Navarro H, Warner KR, Gilmour B . The identification of nonpeptide neurotensin receptor partial agonists from the potent antagonist SR48692 using a calcium mobilization assay . Bioorganic & Medicinal Chemistry Letters . 19 . 5 . 1438–1441 . March 2009 . 19195889 . 4418176 . 10.1016/j.bmcl.2009.01.024 .
- Bredeloux P, Costentin J, Dubuc I . Interactions between NTS2 neurotensin and opioid receptors on two nociceptive responses assessed on the hot plate test in mice . Behavioural Brain Research . 175 . 2 . 399–407 . December 2006 . 17074405 . 10.1016/j.bbr.2006.09.016 . 24790151 .
- Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S, Antonelli T . Neurotensin receptors as modulators of glutamatergic transmission . Brain Research Reviews . 58 . 2 . 365–373 . August 2008 . 18096238 . 10.1016/j.brainresrev.2007.11.001 . 25434443 .
- Attrill H, Harding PJ, Smith E, Ross S, Watts A . Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies. . Protein Expr Purif . 64 . 1 . 32–38 . 2009 . 18976711 . 10.1016/j.pep.2008.10.001 .
- Harding PJ, Hadingham TC, McDonnell JM, Watts A . Direct analysis of a GPCR-agonist interaction by surface plasmon resonance. . Eur Biophys J . 35 . 8 . 709–712 . 2006 . 16708210 . 10.1007/s00249-006-0070-x . 7844675 .
- Harding PJ, Attrill H, Boehringer J, Ross S, Wadhams GH, Smith E, Armitage JP, Watts A . Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers. . Biophys. J. . 96 . 3 . 964–973 . 2009 . 19186134 . 10.1016/j.bpj.2008.09.054 . 2716571. 2009BpJ....96..964H .
- Selmi DN, Adamson RJ, Attrill H, Goddard AD, Gilbert RJ, Watts A, Turberfield AJ . DNA-templated protein arrays for single-molecule imaging. . Nano Lett. . 11 . 2 . 657–660 . 2011 . 21218848 . 10.1021/nl1037769 . 2011NanoL..11..657S .
