Neurotensin receptor

neurotensin receptor 1 (high affinity)
Identifiers
Symbol	NTSR1
Alt. symbols	NTR
NCBI gene	4923
HGNC	8039
OMIM	162651
RefSeq	NM_002531
UniProt	P30989
Other data
Locus	Chr. 20 q13-20q13
Search for Structures Swiss-model Domains InterPro

neurotensin receptor 2
Identifiers
Symbol	NTSR2
Alt. symbols	NTR2
NCBI gene	23620
HGNC	8040
OMIM	605538
RefSeq	NM_012344
UniProt	O95665
Other data
Locus	Chr. 2 p25.1
Search for Structures Swiss-model Domains InterPro

sortilin 1
Identifiers
Symbol	SORT1
Alt. symbols	Gp95, NT3
NCBI gene	6272
HGNC	11186
OMIM	602458
RefSeq	NM_002959
UniProt	Q99523
Other data
Locus	Chr. 1 p21.3-1p13.1
Search for Structures Swiss-model Domains InterPro

Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin. ^{[1] [2]} Two of the receptors encoded by the NTSR1 and NTSR2 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 SORT1 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

• Levocabastine (NTS₂ selective, also H₁ histamine antagonist) ^[6]
• SR-48692 (NTS₁ selective) ^[7]
• SR-142948 (unselective, CAS# 184162-64-9)

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]

References

1. Vincent JP, Mazella J, Kitabgi P (1999). "Neurotensin and neurotensin receptors". Trends Pharmacol. Sci. 20 (7): 302–309. doi:10.1016/S0165-6147(99)01357-7. PMID   10390649.
2. Pelaprat D (2006). "Interactions between neurotensin receptors and G proteins". Peptides. 27 (10): 2476–2487. doi:10.1016/j.peptides.2006.04.027. PMID   16919370. S2CID   21730838.
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 (January 2021). "Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism". Science Advances. 7 (5) eabe5504. Bibcode:2021SciA....7.5504D. doi:10.1126/sciadv.abe5504. PMC   7840143 . PMID   33571132.
4. Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M (April 2003). "Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist". Bioscience, Biotechnology, and Biochemistry. 67 (4): 940–3. doi: 10.1271/bbb.67.940 . PMID   12784648. S2CID   83609327.
5. Thomas JB, Navarro H, Warner KR, Gilmour B (March 2009). "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. doi:10.1016/j.bmcl.2009.01.024. PMC   4418176 . PMID   19195889.
6. Bredeloux P, Costentin J, Dubuc I (December 2006). "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. doi:10.1016/j.bbr.2006.09.016. PMID   17074405. S2CID   24790151.
7. Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S, Antonelli T (August 2008). "Neurotensin receptors as modulators of glutamatergic transmission". Brain Research Reviews. 58 (2): 365–373. doi:10.1016/j.brainresrev.2007.11.001. PMID   18096238. S2CID   25434443.
8. Attrill H, Harding PJ, Smith E, Ross S, Watts A (2009). "Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies". Protein Expr Purif. 64 (1): 32–38. doi:10.1016/j.pep.2008.10.001. PMID   18976711.
9. Harding PJ, Hadingham TC, McDonnell JM, Watts A (2006). "Direct analysis of a GPCR-agonist interaction by surface plasmon resonance". Eur Biophys J. 35 (8): 709–712. doi:10.1007/s00249-006-0070-x. PMID   16708210. S2CID   7844675.
10. Harding PJ, Attrill H, Boehringer J, Ross S, Wadhams GH, Smith E, Armitage JP, Watts A (2009). "Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers". Biophys. J. 96 (3): 964–973. Bibcode:2009BpJ....96..964H. doi:10.1016/j.bpj.2008.09.054. PMC   2716571 . PMID   19186134.
11. Selmi DN, Adamson RJ, Attrill H, Goddard AD, Gilbert RJ, Watts A, Turberfield AJ (2011). "DNA-templated protein arrays for single-molecule imaging". Nano Lett. 11 (2): 657–660. Bibcode:2011NanoL..11..657S. doi:10.1021/nl1037769. PMID   21218848.

External links

• "Neurotensin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2007-04-24.
• Neurotensin+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)