Disease relevance of Ntsr1

• Parallel studies carried out on Sf9 insect cells expressing the rat neurotensin receptor from a recombinant baculovirus indicated that the internalization process involves receptor-ligand complexes and not merely the fluorescent peptide itself [1].
• This suggested that nonpeptide agonist mimetics acting at the NTR1 might be helpful in the treatment of Parkinson's disease and schizophrenia [2].
• Replacement of the last three amino acids by the cytoplasmic endocytosis signal of the vesicular stomatitis virus did not restore the efficiency of neurotensin receptor internalization [3].
• Expression of a rat neurotensin receptor in Escherichia coli [4].
• Evidence for the dual coupling of the rat neurotensin receptor with pertussis toxin-sensitive and insensitive G-proteins [5].

Psychiatry related information on Ntsr1

• The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg [6].

High impact information on Ntsr1

• Chronic neuroleptic treatment enhances neurotensin receptor binding in human and rat substantia nigra [7].
• This investigation discloses the molecular nature of the neurotensin receptor, which mediates the diverse neuronal and peripheral actions of neurotensin by effecting the G protein-associated second messenger system [8].
• A functional cDNA clone for the rat neurotensin receptor was isolated by combining molecular cloning in an RNA expression vector with an electrophysiological assay in Xenopus oocytes [8].
• Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression [9].
• Correlative ultrastructural distribution of neurotensin receptor proteins and binding sites in the rat substantia nigra [10].

Chemical compound and disease context of Ntsr1

• With the goal of obtaining sufficient quantities of seven-helix G-protein-coupled receptors for structural analysis, we have studied the functional expression of a rat neurotensin receptor cDNA in Escherichia coli with and without a signal sequence and as a fusion with the gene coding for maltose-binding protein [4].
• Central administration of the neurotensin receptor antagonist SR48692 attenuates vacuous chewing movements in a rodent model of tardive dyskinesia [11].
• The possible modulation of the glutamate transporter EAAC1 by a class A G protein-coupled receptor was studied in transfected C6 glioma cells stably expressing the high-affinity neurotensin receptor NTS1 [12].
• These results indicate that the transfected cells actively express the rat neurotensin receptor which is functionally coupled to phospholipase C through a pertussis toxin-insensitive GTP-binding protein, and that neuromedin N is able to induce the phosphoinositides turnover by interaction with the neurotensin receptor [13].

Biological context of Ntsr1

• In the present study we attempted, through mutagenesis and computer-assisted modeling, to identify residues in the rat NTR1 that are involved in antagonist binding and to provide a tentative molecular model of the SR 48692 binding site [14].
• In order to identify the amino acid sequences responsible for the internalization of the cloned rat brain neurotensin receptor, we carried out site-directed mutagenesis of the cDNA encoding the receptor followed by expression of the receptor into mammalian COS 7 cells [3].
• Our results led us to propose a region of the neurotensin receptor that may be involved in determining species specificity, i. e. the transmembrane VI, the third extracellular loop, and transmembrane VII regions of the neurotensin receptor [15].
• Furthermore, our data show that neurotensin receptor sequestration is independent of agonist-induced polyphosphoinositide hydrolysis [16].
• The two different signal transduction systems may be induced by different G proteins that couple at different sites of the neurotensin receptor protein in CHO-K1 cells [16].

Anatomical context of Ntsr1

• Recycling of the neurotensin receptor-2 involves both the phosphatidylinositol 3-kinase and the recycling endosome pathways, whereas recycling of the neurotensin receptor-1 induced by overexpression of NEEP21 only occurs by the phosphatidylinositol 3-kinase-dependent pathway [17].
• Lack of rapid desensitization of Ca2+ responses in transfected CHO cells expressing the rat neurotensin receptor despite agonist-induced internalization [18].
• Quantitative OD analysis showed haloperidol-induced NTR mRNA levels in the substantia nigra/ventral tegmental area (SN/VTA) 110% over control levels (significant difference from the control, p < 0.05) [19].
• These results suggest that the relation between structure and function of the neurotensin receptor can be readily studied in transfected cell lines [20].
• Stable expression of the cloned rat brain neurotensin receptor into fibroblasts: binding properties, photoaffinity labeling, transduction mechanisms, and internalization [21].

Associations of Ntsr1 with chemical compounds

• The striatal neurotensin receptor modulates striatal and pallidal glutamate and GABA release: functional evidence for a pallidal glutamate-GABA interaction via the pallidal-subthalamic nucleus loop [22].
• The data also show that the agonist and antagonist binding sites in the rNTR1 are different and help formulate hypotheses as to the structural basis for the selectivity of SR 48692 toward the NTR1 and NTR2 [14].
• Primary cultures of cortical neurons were employed to investigate the modulatory effects of neurotensin on glutamate excitotoxicity and the possible neuroprotective actions of the neurotensin receptor antagonist SR48692 [23].
• Neurotensin enhances endogenous extracellular glutamate levels in primary cultures of rat cortical neurons: involvement of neurotensin receptor in NMDA induced excitotoxicity [23].
• Deletion mutation in the putative third intracellular loop of the rat neurotensin receptor abolishes polyphosphoinositide hydrolysis but not cyclic AMP formation in CHO-K1 cells [16].

Physical interactions of Ntsr1

• Identification of residues involved in neurotensin binding and modeling of the agonist binding site in neurotensin receptor 1 [2].

Regulatory relationships of Ntsr1

• The decrease in neurotensin receptor number was also induced by the active fragment (8-13) of neurotensin but not by its inactive fragment (1-8) [24].
• In this study, we demonstrated that the tyrosine hydroxylase-like immuno-reactive (possibly dopaminergic) neurons express neurotensin receptor mRNA in the rat substantia nigra and in the ventral tegmental area [25].

Other interactions of Ntsr1

• Microdialysis was employed to investigate the dopamine, cholecystokinin (CCK) and neurotensin receptor regulation of ventral striopallidal GABA transmission by intra-accumbens perfusion with selective receptor ligands and monitoring local or ipsilateral ventral pallidal GABA release [26].
• Neurotensin receptor antagonist SR 142948A alters Fos expression and extrapyramidal side effect profile of typical and atypical antipsychotic drugs [27].
• The study of the pharmacological, biochemical, and transduction properties of the cloned rat brain neurotensin receptor was carried out in thymidine kinase mutant fibroblasts stably transfected with the receptor cDNA [21].
• For immunological detection and future purification of neurotensin receptor, a C-terminal pentahistidine/c-myc tail was introduced [4].
• 1. The neurotensin receptor 1, NTS1, is a G protein-coupled receptor with seven transmembrane domains (TM) that mediates most of the known effects of the neuropeptide [28].

Analytical, diagnostic and therapeutic context of Ntsr1

• In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand [29].
• We examined the effects of chronic (2 weeks) treatment with a typical neuroleptic, haloperidol (1 mg/kg, s.c.), and an atypical neuroleptic, clozapine (20 mg/kg, s.c.), on neurotensin receptor (NTR) mRNA levels by in situ hybridization histochemistry [19].
• We also show that microinjection of NT or the NTR1-selective agonist PD149163 in the RVM both produce dose-dependent antinociception in the tail-flick test that is blocked by the NTR1-selective antagonist SR48692 [30].
• Western-blot analysis revealed the association of neurotensin receptor with E. coli membranes [4].
• The subcellular localization of neurotensin-receptor sites (NT2 sites) and neurotensin-acceptor sites (NT1 sites) was studied in rat caudate-putamen by isopycnic centrifugation in sucrose density gradients [31].

References