Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to investigate the regulation by insulin-like growth factors 1 and 2, and interleukins on the production of neurotensin in the SH-SY5Y cell line derived from a human neuroblastoma. Cultures were performed in RPMI1640 culture medium with heated foetal calf serum 12%. After 24 hrs. of fasting without serum, interleukins-1 alpha, IL-2, IL-4 and insulin-like growth factors 1 and 2 were added. Results showed: 1) A mitogenic effect of ILs (p < 0.001) and of IGFs (p < 0.001). 2) The presence of neurotensin in HCl0.1N cellular extracts (0.06 fmol/micrograms protein). 3) The increase of cellular neurotensin content in the presence of IL-4 (560%), IL-2 (480%), IGF-1 (610%) and IGF-2 (200%). Our results indicate that the human neuroblastoma cell line SH-SY5Y produces neurotensin and that ILs and IGFs act in vitro to modulate this production.
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PMID:[Effect of interleukins and somatomedins on the production of neurotensin by cell line SH-SY5Y derived from human neuroblastoma]. 129 57

We have demonstrated that the aminosteroid, U-73122 (1-(6-([17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl)-1H-pyrrole- 2,5-dione) blocks agonist induced down-regulation of neurotensin receptors in murine neuroblastoma clone N1E-115 cells. U-73122 is known to inhibit polyphosphoinositide hydrolysis by affecting the coupling of GTP-binding proteins. Our results may indicate that GTP-binding proteins play a role in the mechanism of down-regulation of the neurotensin receptor.
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PMID:Block of neurotensin receptor down-regulation by an aminosteroid in N1E-115 cells. 132 8

To study second messenger synthesis mediated by the cloned rat neurotensin receptor, we derived a cell line stably expressing this receptor. The cDNA clone of this receptor was subcloned into the pcDNA1neo expression vector. This construct was then used to transfect Chinese hamster ovary (CHO)-K1 cells. Colony clones, selected for resistance to antibiotic G-418 sulfate, were isolated and grown separately. Nineteen individual clones were screened for total [3H]neurotensin binding as an indication of neurotensin receptor expression. The clone (CHO-rNTR-10) showing the highest level of specific [3H]neurotensin binding was characterized further. With intact cells, the equilibrium dissociation constant (KD) for specific [3H]neurotensin binding was 18 nM, and the maximal number of binding sites (Bmax) was 900 fmol/mg of protein or 740 fmol/10(6) cells (approximately 4.4 x 10(5) sites on the cellular surface). Whereas the KD was similar to that found in other cellular systems, for example, the murine neuroblastoma clone N1E-115, the Bmax exceeded previously reported values. Incubation of intact CHO-rNTR-10 cells with neurotensin caused the release of inositol phosphates in a dose-dependent manner (EC50 = 3 nM), results indicating that the expressed transfected receptor was functional. Neurotensin did not inhibit cyclic AMP levels stimulated by forskolin. As with other systems, neurotensin (8-13) was more potent than neurotensin Neurotensin-mediated inositol phosphate release is the first report of second messenger synthesis for this receptor expressed in a transfected cell line. These results suggest that the relation between structure and function of the neurotensin receptor can be readily studied in transfected cell lines.
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PMID:The rat neurotensin receptor expressed in Chinese hamster ovary cells mediates the release of inositol phosphates. 132 36

Endothelial cells (ECs) from brain microvessels respond to exogenous nitric oxide (NO) donor molecules (N-ethoxycarbonyl-3-morpholinosydnonimine and sodium nitroprusside) with large (greater than 15-fold) increases in cyclic GMP (cGMP) levels. Comparable actions of sodium nitroprusside were observed in vascular smooth muscle cells and in neuroblastoma cells. Coculturing brain capillary ECs in the presence of N1E-115 neuroblastoma cells increased their cGMP levels fourfold. A further increase was observed in the presence of 50 nM neurotensin, although brain capillary ECs lack receptor sites for neurotensin. The neuroblastoma cell-dependent formation of cGMP was suppressed by 0.1 mM L-NG-monomethylarginine, indicating that NO, produced by N1E-115 cells in response to neurotensin, activated guanylate cyclase in brain capillary ECs. Similarly, culturing brain capillary ECs in the presence of aortic ECs increased their cGMP content in a manner that was amplified by bradykinin and that was inhibited by L-NG-monomethylarginine. Bradykinin had no action in pure cultures of brain capillary ECs. It is concluded that brain capillary ECs express high levels of guanylate cyclase activity that could be activated by exogenous NO donor molecules and by NO produced by neuroblastoma cells and by aortic ECs in response to specific agonists. Brain capillary ECs are thus potential target cells for brain-derived NO.
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PMID:Activation by nitric oxide of guanylate cyclase in endothelial cells from brain capillaries. 135 91

Neurotensin is a tridecapeptide with changing receptor expression in central and peripheral neural cells during ontogeny suggesting its potential use as a differentiation and tumor marker in neuroectodermal malignancies. We investigated the neurotensin levels in plasma samples of 58 patients with neuroblastoma using a sensitive radioimmunoassay. Elevated levels were found only in one stage III and in one stage IVs patient, while the neurotensin concentrations of 56 patients were in the range of control children. We conclude that plasma neurotensin reflects neither the differentiation nor the tumor status in children with neuroblastoma.
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PMID:Plasma neurotensin: lack of a differentiation and tumor marker in children with neuroblastoma. 152 6

Murine neuroblastoma cells (clone N1E-115) during their growth from log to late stationary phase, expressed no specific neurotensin binding sites until day 7 in culture. From day 7 to day 20, binding sites increased 6-fold in number/cell and more than 4-fold in sites/mg protein. Neurotensin-mediated cyclic [3H]GMP synthesis was not detected until day 17. For these cells these data show that neurotensin receptor binding and function are regulated with respect to growth cycle and that presence of neurotensin binding sites is not sufficient for receptor function.
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PMID:Developmental regulation of neurotensin receptor expression and function in murine neuroblastoma clone N1E-115. 165 92

Neurotensin, an endogenous tridecapeptide, produces a potent, naloxone-insensitive antinociceptive response when it is microinjected into the periaqueductal gray region of the rat brainstem. In the present study, the ED50 for neurotensin in inducing antinociception was 1.5 nmol, two times more potent than morphine. We sought to find whether neurotensin's antinociceptive effects were mediated by the same receptor that mediates its other functions. We found that the structure-activity relationship of neurotensin-induced antinociception was different from that required for the stimulation of intracellular cyclic GMP production in neuroblastoma clone N1E-115 and the binding to N1E-115 cells, human brain tissue, or rat periaqueductal gray. These data suggest there exists a subtype of neurotensin receptors in neural tissue that mediates its antinociceptive actions.
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PMID:Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem. 166 Jul 54

There is considerable literature on the pathogenesis of tetanus toxin poisoning; however, the mechanism of action and intracellular substrate of this toxin have not been defined. It was demonstrated that the NG-108 neuroblastoma x glioma cell line is a suitable model in which to study the mechanism of tetanus toxin action, from binding of the toxin to inhibition of transmitter release. Further, it has been shown that tetanus toxin pretreatment attenuates the ability of phorbol myristate acetate to mobilize cytosolic protein kinase C (PKC) in this cell line. In the present study a 4-hr tetanus toxin pretreatment (10(-10)-10(-13) M) completely inhibited the mobilization of cytosolic PKC induced by a 30-min exposure to 10 microM neurotensin. Pretreatment with 10(-10) M tetanus toxin for periods as short as 1 hr was sufficient to attenuate the ability of neurotensin to mobilize cytosolic PKC; however, a 30-min pretreatment had no significant effect. At a concentration of 10(-11) M, it was necessary to pretreat the cells for greater than 1 hr to significantly attenuate neurotensin-mobilized PKC activity. The exact role that PKC plays in the secretory process is not yet known; however, these findings suggest that the effect of tetanus toxin on neurotransmitter release is accompanied by an alteration in PKC metabolism in differentiated NG-108 cells.
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PMID:Tetanus toxin inhibits neurotensin-induced mobilization of cytosolic protein kinase C activity in NG-108 cells. 181 11

Both ethanol and neurotensin produce sedation and hypothermia. When administered in combination the behavioral effects of these two substances are potentiated. In order to better understand the biochemical nature of this interaction, the direct effects of ethanol on neurotensin receptors and an associated signal transduction process were determined in NIE-115 neuroblastoma cells. Ethanol in physiologically relevant concentrations (50mM) significantly reduced neurotensin stimulated [3H]inositol phosphate production while having no effect on the specific binding of [3H]neurotensin. In addition, ethanol up to 200 mM had no effect on GTPYS mediated [3H]inositol phosphate production. The results indicate that acute exposure to ethanol partially disrupts the normal coupling of activated neurotensin receptors to the guanine nucleotide binding protein associated with phospholipase C.
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PMID:The effects of acute exposure to ethanol on neurotensin and guanine nucleotide-stimulation of phospholipase C activity in intact NIE-115 neuroblastoma cells. 217 77

Mouse neuroblastoma x rat glioma hybrid NG108-15 cells form cholinergic synapses with rat or mouse muscle cells in culture. The rate of synapse formation is greatly dependent on intracellular cyclic AMP concentrations. The synapse formation is lower in the presence of glia maturation factor, a partially purified brain extract. Once the synapse between NG108-15 cells and myotubes has been formed, this synapse is stable for days. Extracellular application of serotonin, PGF2 alpha, PGD2, neurotensin and bradykinin on NG108-15 cells increases synaptic transmission. Since bradykinin increases the level of intracellular inositol 1,4,5-trisphosphate (InsP3), bradykinin-induced facilitation is due to InsP3-dependent elevation of intracellular Ca concentrations.
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PMID:Cholinergic synapse formation between NG108-15 and muscle cells and modulation of transmission. 217 13


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