Neurotensin receptor

neurotensin receptor 2
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
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

neurotensin receptor 1 (high affinity)
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
Structures
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Structures	Swiss-model
Domains	InterPro

sortilin 1

Identifiers

Symbol

SORT1

Alt. symbols

Gp95, NT3

Other data

Chr. 1 p21.3-1p13.1

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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

^ 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.
^ 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.
^ ^a ^b ^c 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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)