Neurotensin Receptor

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

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

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

Short description: InterPro Family

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

↑ "Neurotensin and neurotensin receptors". Trends Pharmacol. Sci. 20 (7): 302–309. 1999. 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. http://www.hal.inserm.fr/inserm-00519739/document.
↑ ^3.0 ^3.1 ^3.2 "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. doi:10.1126/sciadv.abe5504. PMID 33571132. Bibcode: 2021SciA....7.5504D.
↑ "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. doi:10.1271/bbb.67.940. PMID 12784648. http://joi.jlc.jst.go.jp/JST.JSTAGE/bbb/67.940?lang=en&from=PubMed.
↑ "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. doi:10.1016/j.bmcl.2009.01.024. PMID 19195889.
↑ "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. doi:10.1016/j.bbr.2006.09.016. PMID 17074405.
↑ "Neurotensin receptors as modulators of glutamatergic transmission". Brain Research Reviews 58 (2): 365–373. August 2008. doi:10.1016/j.brainresrev.2007.11.001. PMID 18096238.
↑ "Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies.". Protein Expr Purif 64 (1): 32–38. 2009. doi:10.1016/j.pep.2008.10.001. PMID 18976711.
↑ "Direct analysis of a GPCR-agonist interaction by surface plasmon resonance.". Eur Biophys J 35 (8): 709–712. 2006. doi:10.1007/s00249-006-0070-x. PMID 16708210.
↑ "Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.". Biophys. J. 96 (3): 964–973. 2009. doi:10.1016/j.bpj.2008.09.054. PMID 19186134. Bibcode: 2009BpJ....96..964H.
↑ "DNA-templated protein arrays for single-molecule imaging.". Nano Lett. 11 (2): 657–660. 2011. doi:10.1021/nl1037769. PMID 21218848. Bibcode: 2011NanoL..11..657S.

External links

"Neurotensin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1342.
Neurotensin+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

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Original source: https://en.wikipedia.org/wiki/Neurotensin receptor. Read more

[pmid10390649-1] "Neurotensin and neurotensin receptors". Trends Pharmacol. Sci. 20 (7): 302–309. 1999. doi:10.1016/S0165-6147(99)01357-7. PMID 10390649.

[pmid16919370-2] 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. http://www.hal.inserm.fr/inserm-00519739/document.

[pmc=7840143-3] 3.0 ^3.1 ^3.2 "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. doi:10.1126/sciadv.abe5504. PMID 33571132. Bibcode: 2021SciA....7.5504D.

[pmid12784648-4] "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. doi:10.1271/bbb.67.940. PMID 12784648. http://joi.jlc.jst.go.jp/JST.JSTAGE/bbb/67.940?lang=en&from=PubMed.

[pmid19195889-5] "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. doi:10.1016/j.bmcl.2009.01.024. PMID 19195889.

[pmid17074405-6] "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. doi:10.1016/j.bbr.2006.09.016. PMID 17074405.

[pmid18096238-7] "Neurotensin receptors as modulators of glutamatergic transmission". Brain Research Reviews 58 (2): 365–373. August 2008. doi:10.1016/j.brainresrev.2007.11.001. PMID 18096238.

[pmid18976711-8] "Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies.". Protein Expr Purif 64 (1): 32–38. 2009. doi:10.1016/j.pep.2008.10.001. PMID 18976711.

[pmid16708210-9] "Direct analysis of a GPCR-agonist interaction by surface plasmon resonance.". Eur Biophys J 35 (8): 709–712. 2006. doi:10.1007/s00249-006-0070-x. PMID 16708210.

[pmid19186134-10] "Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.". Biophys. J. 96 (3): 964–973. 2009. doi:10.1016/j.bpj.2008.09.054. PMID 19186134. Bibcode: 2009BpJ....96..964H.

[pmid21218848-11] "DNA-templated protein arrays for single-molecule imaging.". Nano Lett. 11 (2): 657–660. 2011. doi:10.1021/nl1037769. PMID 21218848. Bibcode: 2011NanoL..11..657S.