Neurotensin

Overview: Neurotensin receptors (provisional nomenclature) are activated by the endogenous tridecapeptide neurotensin (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) derived from a precursor (ENSG00000133636), which also generates neuromedin N, an agonist at the NTS₂ receptor. A non-peptide antagonist, SR142948A, shows high affinity (pK_i∼9) at both NTS₁ and NTS₂ receptors (Gully et al., 1997). [³H]-Neurotensin and [¹²⁵I]-neurotensin may be used to label NTS₁ and NTS₂ receptors at 0.1–0.3 and 3–5 nM concentrations respectively.

Nomenclature	NTS1	NTS2
Other names	High-affinity neurotensin receptor, NTRH, NTR-1, NT1	Low-affinity neurotensin receptor, NTRL, NTR-1, NT2
Ensembl ID	ENSG00000101188	ENSG00000169006
Principal transduction	Gq/11	Gq/11
Rank order of potency	Neurotensin > neuromedin N (Hermans et al. (1997)	Neurotensin = neuromedin N (Mazella et al., 1996)
Selective agonists	JMV449 (Souaze et al., 1997)	Levocobastine (Mazella et al., 1996)
Selective antagonists	SR48692 (7.5–8.2; Gully et al., 1997)	–
Probes	[3H]-SR48692 (3.4 nM; Labbe-Jullie et al., 1995)	–

Neurotensin appears to be a low-efficacy agonist at the NTS₂ receptor (Vita et al., 1998), while the NTS₁ receptor antagonist SR48692 is an agonist at NTS₂ receptors (Vita et al., 1998). An additional protein, provisionally termed NTS3 (also known as NTR3, gp95 and sortilin; ENSG00000134243), has been suggested to bind lipoprotein lipase and mediate its degradation (Nielsen et al., 1999). It has been reported to interact with the NTS₁ receptor (Martin et al., 2002) and has been implicated in hormone trafficking and/or neurotensin uptake.

Glossary

Abbreviations:

JMV449

H-Lysψ (CH₂NH)-Lys-Pro-Tyr-Ile-Leu

SR142948A

2-([5-{2,6-dimethoxyphenyl}-1-{4-(N-[3-dimethylaminopropyl]-N-methylcarbamoyl)-2-isopropylphenyl}-1H-pyrazole-3-carbonyl]amino)adamantane-2-carboxylic acid hydrochloride

SR48692

2-([1-{7-chloro-4-quinolinyl}-5-{2,6-dimethoxyphenyl}pyrazol-3-yl]carboxylamino)tricyclo(3.3.1.1.[3.7])decan-2-carboxylic acid

Further Reading

Antonelli T, Fuxe K, Tomasini MC, Mazzoni E, Agnati LF, Tanganelli S et al. (2007). Neurotensin receptor mechanisms and its modulation of glutamate transmission in the brain: relevance for neurodegenerative diseases and their treatment. Prog Neurobiol83: 92–109.

Boules M, Shaw A, Fredrickson P, Richelson E (2007). Neurotensin agonists: potential in the treatment of schizophrenia. CNS Drugs21: 13–23.

Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S et al. (2008). Neurotensin receptors as modulators of glutamatergic transmission. Brain Res Rev58: 365–373.

Hwang JI, Kim DK, Kwon HB, Vaudry H, Seong JY (2009). Phylogenetic history, pharmacological features, and signal transduction of neurotensin receptors in vertebrates. Ann N Y Acad Sci1163: 169–178.