Disease relevance of NTS

• We have shown that SK-N-SH neuroblastoma cells express NTR1 and NTR3 but not NTR2, suggesting that the Ca2+ mobilization elicited by R-NT is via NTR1 [1].
• Neurotensin causes relaxation of the gallbladder in humans and, by contributing to stasis, may be involved in the formation of gallstones [2].
• High levels of bombesin (BB) and neurotensin (NT)-like immunoreactivity are present in small cell lung cancer (SCLC), a neuroendocrine tumor [3].
• Inhibition of mitochondrial gene transcription suppresses neurotensin secretion in the human carcinoid cell line BON [4].
• In this study we demonstrated an anti-apoptotic effect of NT agonist, in the mammary adenocarcinoma cells, MCF-7 [5].

Psychiatry related information on NTS

• Mutational analysis of neurotensin in familial restless legs syndrome [6].
• Plasma cholecystokinin and neurotensin after an ordinary meal in humans. A prolonged time study [7].
• Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied [8].
• Nicoderm, a nicotine transdermal system (NTS), provides a continuous, transdermal delivery of nicotine and is used as an aid to smoking cessation [9].
• To ascertain whether Huntington's chorea and schizophrenia are associated with specific regional alterations in neurotensin, somatostatin, and thyrotropin-releasing hormone, the concentrations of these putative neurotransmitters were measured by radioimmunoassay in postmortem brain samples from patients with Huntington's chorea or schizophrenia [10].

High impact information on NTS

• Environmental 131I contamination from atmospheric nuclear bomb tests conducted at the NTS from 1951 to 1958 exposed Americans nationwide to a cumulative average dose of 1 to 4 rad to the thyroid gland [11].
• Co-localization of neurotensin-like immunoreactivity and 3H-glycine uptake system in sustained amacrine cells of turtle retina [12].
• Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro [13].
• Other emerging and promising peptides and their respective receptors, including neurotensin, substance P, and neuropeptide Y, are introduced [14].
• Neurotensin and dopamine interactions [15].

Chemical compound and disease context of NTS

• BON cells, a novel human carcinoid cell line that produces and secretes NT peptide and expresses the gene encoding NT (designated NT/N), were treated with ethidium bromide (EB; 0.05, 0.1, and 0.4 microg/ml), an inhibitor of DNA and RNA synthesis, or vehicle over a time course (1-4 days) [4].
• A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development [16].
• Stimulation of vasoactive intestinal peptide and neurotensin secretion by pentagastrin in a patient with VIPoma syndrome [17].
• To characterize the properties of the antibody fragment, human and rat high-affinity neurotensin receptors were expressed in E. coli in functional form, linked at their N-termini to the maltose-binding protein [18].
• The gene encoding the gut hormone neurotensin/neuromedin N (NT/N) is expressed in the adult small bowel, and NT/N is transiently expressed in the fetal liver, suppressed in the adult liver, and reexpressed in certain liver cancers [19].

Biological context of NTS

• Using PANC-1 as a model system, we demonstrate that neurotensin (NT) induced a rapid and striking activation of PKD as determined by in vitro kinase assay and by in vivo phosphorylation of serines 744, 748, and 916 [20].
• Whether the NT expressing neurons play a role in generating circadian rhythms in the early life of humans needs to be further investigated [21].
• Recombinant hNT1-R-producing cells, which lacked the endogenous G-protein-coupled receptor for the alpha pheromone, mated with wild-type MATalpha haploid cells in response to neurotensin, leading to bona fide diploid zygote formation [22].
• We now confirm this assignment and place the NTS gene on the physical and cytogenetic maps [23].
• The NTS gene is located on a yeast artificial chromosome contig that contains several polymorphic markers and is close to a polymorphic marker located at 95.8 cM on the Généthon linkage map [23].

Anatomical context of NTS

• Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1 [20].
• NT induced a rapid and transient translocation of PKD from the cytosol to the plasma membrane [20].
• OBJECTIVE: The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland [24].
• Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines [25].
• NT terminal plexuses were particularly abundant in layers I-VI of the anterior cingulate cortex, in layer I of area 32 and of medical areas 9, 8, 6 and in layers II-III of area 29, of the presubiculum and entorhinal cortex [25].

Associations of NTS with chemical compounds

• PKD activation induced by NT was abrogated by treatment of PANC-1 cells with PKC inhibitors GF-1 and Ro 31-8220 [20].
• Rho protein inhibitor C3 dramatically inhibited both NT secretion and PKD activity [26].
• In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m [24].
• Competition binding studies of neurotensin with SR142948 and SR48692, two nonpeptidic antagonists of hNT1-R, indicated that the yeast-produced recombinant receptor displayed the same pharmacological properties as hNT1-R expressed in mammalian cells [22].
• Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus [21].

Physical interactions of NTS

• Neurotensin (NT) is a neuropeptide interacting with specific G protein coupled receptors [5].
• Activation of mitogen-activated protein kinase couples neurotensin receptor stimulation to induction of the primary response gene Krox-24 [27].

Enzymatic interactions of NTS

• ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested [28].
• Thimet oligopeptidase mutated so that neurolysin residues are at all four positions cleaves neurotensin at the neurolysin site, and the reverse mutations in neurolysin switch hydrolysis to the thimet oligopeptidase site [29].

Regulatory relationships of NTS

• Neurotensin induces mating in Saccharomyces cerevisiae cells that express human neurotensin receptor type 1 in place of the endogenous pheromone receptor [22].
• Furthermore, inhibition of PKC-alpha and -delta blocked PMA-stimulated NT secretion, suggesting a critical role for these isoforms in NT release [30].
• These results indicate that modulation of tyrosine hydroxylase gene expression may constitute one of the mechanisms involved in the control of dopamine transmission by neurotensin [31].
• We speculate that a complex pattern of regulation requiring interaction between a proximal CRE/AP-1-like motif and other upstream control elements play an important role in the high-level constitutive expression of NT/N in the human endocrine cell line BON [32].
• Cell stimulation with the GPCR agonist neurotensin induced a rapid and reversible plasma membrane translocation of PKD3 that is PKC-dependent [33].

Other interactions of NTS

• No significant intergroup differences were noted in postprandial levels of Nt and CCK [34].
• Collectively our results demonstrate, for the first time, the existence of a functional PKC/PKD signaling pathway in human ductal pancreatic carcinoma cells and suggest that PKCs mediate the mitogenic signaling process initiated by NT [20].
• BBS-mediated NT secretion was attenuated by MARCKS siRNA [35].
• A few varicose fibers were labeled with antisera against neurotensin (NT), leucine-enkephalin (L-ENK), and the vasoactive intestinal polypeptide (VIP) [36].
• Even in zones where TH and NT innervations were abundant, such as the anterior cingulate cortex or area 32, double-labeling procedures disclosed no colocalized fibers [25].

Analytical, diagnostic and therapeutic context of NTS

• HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts [24].
• We expressed the intracellular receptor NTR3 as a soluble protein secreted into the cell culture medium, which allowed characterization of its R-NT and neurotensin binding properties [1].
• Intravenous infusion of neurotensin produced dilatation of the gallbladder (from a mean basal volume of 13.7 +/- 2.3 cc to 20.0 +/- 1.8 cc) [2].
• We determined the effects of infused neurotensin (4 pmol/kg-min) on gallbladder contractility, measured by ultrasonography in 10 adult volunteers, and we evaluated release of neurotensin in eight patients with gallstones [2].
• Measurement of immunoreactive peptide levels with radioimmunoassay, and visualization of peptidergic neurons and fibers with immunocytochemistry has demonstrated not only that peptides exist in the vicinity of A10 dopamine neurons, but using double labeling techniques NT and CCK have been found to coexist with dopamine in the same neuron [37].

References