Disease relevance of Ntsr1

• Equally intriguing, was that NT24, a sterioisomer of NT27, with a much higher affinity (KD=0. 5 nM) at NTR-1, did not selectively induce hypothermia in mice, but did selectively induce hypothermia in rats [1].
• NT-1R(-/-) mice showed a small significant increase in body weight compared to the NT-1R(+/+) congeners as early as 10 weeks after birth, correlated with a higher food intake [2].
• Sequences required for induction of neurotensin receptor gene expression during neuronal differentiation of N1E-115 neuroblastoma cells [3].
• Thus, being a potent and selective neurotensin receptor antagonist, SR 48692 may be considered as a powerful tool for investigating the role of neurotensin in physiological and pathological processes [4].
• Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression [5].

Psychiatry related information on Ntsr1

• In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in different behavioural tests of locomotor activity using vehicle, amphetamine, or haloperidol in mice [6].

High impact information on Ntsr1

• We describe the characteristics of SR 48692, a selective, nonpeptide antagonist of the neurotensin receptor [4].
• Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity [5].
• This new NT receptor (NTR) type is 39% homologous to, but pharmacologically distinct from, the only other NTR cloned to date from the rat brain and the human HT29 cell line [7].
• Me(2)SO-induced neuronal differentiation of N1E-115 neuroblastoma cells increased both the expression of the endogenous Ntr-1 gene and reporter genes driven by NTR-1 promoter sequences by 3-4-fold [3].
• The promoter region of the mouse high affinity neurotensin receptor (Ntr-1) gene was characterized, and sequences required for expression in neuroblastoma cell lines that express high affinity NT-binding sites were characterized [3].

Chemical compound and disease context of Ntsr1

• This indicates that despite the results with the recently-cloned levocabastine-sensitive NT receptors (NTR) in the rat (NTR-2) and mouse (NTRL), levocabastine by itself does not mediate either hypothermia or antinociception at NT receptors [8].

Biological context of Ntsr1

• The NT-1R(-/-) mice were hyperthermic; their body temperature was not affected by intracerebroventricular (i.c.v.) administration of NT, contrasting with the hypothermia induced in NT-1R(+/+) mice [2].
• These results provide evidence that Ntr-1 gene regulation involves both positive and negative regulatory elements located in the 5'-flanking region and that Ntr-1 gene activation involves the coordinate activation or induction of several factors, including a CACCC box binding complex [3].
• One of the QTL (chromosome 2, 80 cM) for NTR(H) density and hypnotic sensitivity is linked to the NTR(H) gene, Ntsr [9].
• Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sensitivity to ethanol, NTR(H) and low-affinity neurotensin receptor densities and NT-ir levels in LSXSS recombinant inbred strains [9].
• The gene deletion also resulted in the loss of NTR1 expression as determined by reverse transcription-polymerase chain reaction and in situ hybridization [10].

Anatomical context of Ntsr1

• The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM) [11].
• This finding indicates that a large part of the dopamine efflux evoked by neurotensin in the nucleus accumbens of wild-type mice is mediated via NT1R present in the ventral tegmental area [12].
• Here, we show that only the mouse NTR2 recycled to the plasma membrane, whereas the rat NTR1 and the human NTR2 did not [13].
• The binding properties of the purified analogues toward newborn mouse brain homogenate or toward membranes of cells transitorily (COS) or permanently (AA1) transfected with the cloned rat brain neurotensin receptor cDNA were evaluated and compared with those of radiolabeled neurotensin [14].
• Identification and expression of a variant isoform of the levocabastine-sensitive neurotensin receptor in the mouse central nervous system [15].

Associations of Ntsr1 with chemical compounds

• Levocabastine-sensitive neurotensin receptor (NTRL) mRNAs were localized by in situ hybridization in adult and developing mouse brain [16].
• Similar results were obtained in rats and mice pretreated with the high affinity neurotensin receptor (NTR1) antagonist SR 48692 [17].
• Common QTL indicate that genes regulating NT receptor and/or NT-ir expression may be the same as those regulating sensitivity to ethanol [9].
• Desensitization of neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115 [18].
• In contrast, NT-2 had no effect in NTR1 null mice, whereas the hypomotility effect of clonidine was intact [10].

Physical interactions of Ntsr1

• Three subtypes of neurotensin receptor have been described, two members of the heptahelical transmembrane domain G protein-coupled receptor superfamily NT-1R and NT-2R, and NT-3R unrelated to this family [2].
• Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth [19].
• Changes in neurotensin receptor binding in mice after chronic ethanol consumption [20].

Regulatory relationships of Ntsr1

• I.c.v. administration of the orexigenic neuropeptide Y (NPY) stimulated feeding to the same extent in both wild-type and NT-1R(-/-) mice [2].
• Neurotensin(8-13) was, in fact, fifty times more potent than native neurotensin in stimulating intracellular cyclic GMP formation and had an 18-fold higher affinity for the neurotensin receptor on this neuronal cell type [21].
• Role of signal transduction systems in neurotensin receptor down-regulation induced by agonist in murine neuroblastoma clone N1E-115 cells [22].

Other interactions of Ntsr1

• Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception [1].
• To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice [11].
• However, neither an NTR1 antagonist, SR48692, an NTR2 antagonist, levocabastine, nor the two combined affected the basal level and the neurotensin-mediated decrease in DARPP-32 Thr75 phosphorylation [23].
• Two common QTL for NT-ir levels, but not NTR(H) or low-affinity neurotensin receptor receptors, and ethanol-induced hypothermia were observed on chromosomes 4 (43 cM) and 6 (41 cM) [9].
• Recently, sortilin a non G-protein-coupled receptor has been identified as the 100-kDa neurotensin receptor [24].

Analytical, diagnostic and therapeutic context of Ntsr1

• Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia [25].
• Purification of the neurotensin receptor from mouse brain by affinity chromatography [26].
• In vivo biodistribution of a representative (111)In-DTPA-NT peptide analogue in SCID mice bearing NTR-positive human adenocarcinoma (HT29) xenograft shows that the compound was primarily retained in tumor tissue (2.2% ID/g) and the kidneys (4.8% ID/g) at 4 h postinjection [19].
• Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice [27].
• Also, Northern blot analysis demonstrated no expression for the NT receptor in either LoVo tumour cells or xenografted tumours [28].

References