Neurotensin receptor

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.

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
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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
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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
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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]