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 human neuroblastoma cell line SH-SY5Y was used to demonstrate morphine-induced down-regulation and naloxone-induced up-regulation of opiate receptors in a mu receptor containing neuronally derived preparation capable of desensitization to morphine. Chronic exposure to morphine decreased the number but not the affinity of mu opiate receptors in SH-SY5Y cells. Differentiation of the cells with retinoic acid or with the phorbol agent TPA (12-O-tetradecanoyl-phorbol-13-acetate) increased the number of mu receptors. Morphine-induced down-regulation, however, was observed in the absence of differentiation as well as after differentiation with retinoic acid or TPA. The decrease in the number of receptors was related to time of exposure, with a half-maximum disappearance time (T1/2) of about 3 hr during the initial phase. The receptor decrease was near maximum at 24 hr with no further significant change up to 72 hr. The loss of [3H] DAMGO ([3H]Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) binding was also dose-dependent, with reductions occurring at 0.3, 1 and 10 microM. The loss of receptors was dependent on temperature, with reductions at 37 but not 23 degrees C. The down-regulation was blocked by naloxone and the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D(-Trp-)Orn-Thr-Pen-Thr-NH2), but not by the delta antagonist ICI 174864 ([N,N-diallyl-Tyr1,Aib2,3]Leu-enkephalin). Cholinergic ([3H]quinclidinyl benzilate) binding was not affected by the morphine treatment, indicating that the down-regulation was homologous for opiate receptors. In SH-SY5Y cells, unlike other cell models, the opiate antagonist naloxone upregulated mu receptors by more than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mu opiate receptor down-regulation by morphine and up-regulation by naloxone in SH-SY5Y human neuroblastoma cells. 809 44

In membranes from SH-SY5Y human neuroblastoma cells differentiated with retinoic acid, the mu-selective agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) inhibited cAMP formation with an IC50 of 26 nM. Two separate antibodies raised against distinct regions of the Go alpha sequence attenuated the effect of DAMGO by 50-60%, whereas antibodies to Gi alpha 1,2 or Gi alpha 3 reduced the mu-opioid signal insignificantly or to a lesser extent. In contrast, inhibition of adenylyl cyclase by the delta-opioid agonist Tyr-D-Pen-Gly-Phe-D-Pen-OH (DPDPE; Pen = penicillamine) was very sensitive to the Gi alpha 1,2 antibody. In membranes from rat brain striatum, coupling of the mu opioid receptor to adenylyl cyclase was also maximally blocked by antibodies to Go alpha. After long-term treatment of the cells with DAMGO, the content of Go alpha was reduced by 26%, whereas the levels of Gi alpha 1,2, Gi alpha 3, and Gs alpha were unaltered. Addition of Go, purified from bovine brain, to membranes from pertussis toxin-treated SH-SY5Y cells restored the inhibition of adenylyl cyclase by DAMGO to 70% of that in toxin-untreated cells. To comparably restore the effect of DPDPE, much higher concentrations of Go were required. By demonstrating mediation of cAMP-dependent signal transduction by Go, these results describe (i) an additional role for this G protein present at a high concentration in brain, (ii) preferential, although not exclusive, interaction of mu and delta opioid receptors with different G protein subtypes in coupling to adenylyl cyclase, and (iii) reduced levels of Go following chronic opioid treatment of SH-SY5Y cells with mu opioids.
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PMID:Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain. 809 84

Neurotrophins are responsible for the differentiation and survival of neurons in the developing and in the adult nervous system. They bind to specific membrane receptors with tyrosine kinase activity whose prototype is the product of the trkA proto-oncogene. TrkB, a member of this family, is the receptor for the neurotrophins brain derived growth factor (BDNF) and neurotrophins-3, -4/5. In this study, we show that stable expression of the c-erbA proto-oncogene, which encodes the alpha 1-isoform of the nuclear receptor for thyroid hormone (Tr alpha 1) induces the expression of trkB mRNA with a concomitant decrease to undetectable levels of trkA and trkC mRNAs in the mouse neuroblastoma N2a cell line. trkB induction by c-erbA is ligand independent, since addition of T3 had no effect. The induced trkB transcript encodes a functional gp145trkB protein, which is phosphorylated on tyrosine in response to BDNF. Furthermore, induction of trkB mRNA is also caused by transient expression of either TR alpha 1 or beta 1 isoforms. Our results are compatible with the idea that there are certain pathways which are under control of unliganded thyroid hormone receptor, and that one of these pathways results in regulation of trk expression.
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PMID:Unliganded c-erbA/thyroid hormone receptor induces trkB expression in neuroblastoma cells. 813 11

A 58 kDa protein which was phosphorylated on tyrosine residues with morphine was found in human neuroblastoma cells (SK-N-SH cells) by immunoblot with monoclonal anti-phosphotyrosine antibody. The tyrosine phosphorylation was induced by morphine in 5 min in a dose-dependent manner and the increment was completely inhibited by naloxone. A Delta (d) agonist, [D-Pen2,Pen5]-enkephalin (DPDPE), but not a m agonist, [D-Ala2,N-Me-Phe,Gly5-ol]-enkephalin (DAGO), stimulated the phosphorylation and treatment of the cells with pertussis toxin inhibited the phosphorylation by morphine. These data suggest that d receptor-stimulation increases tyrosine phosphorylation of the 58 kDa protein through Gi protein in SK-N-SH cells.
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PMID:Tyrosine phosphorylation of a 58 kDa protein induced by morphine in SK-N-SH cells. 817 14

Employing an expression cloning approach for tyrosine kinase substrates, we have previously isolated the coding sequence for a novel putative EGFR substrate, eps15, from NIH3T3 fibroblasts. Eps15 displayed a receptor-specific pattern of tyrosine phosphorylation in vivo and was able to transform NIH3T3 cells upon overexpression. To gain understanding of eps15 function as well as its role in normal and neoplastic proliferation, we cloned the human eps15 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. The close structural similarity of human eps15 with the murine homologue is indicated by 89% and 90% identity of nucleotide and predicted amino acid sequences, respectively. Using the human eps15 coding sequence as probe, we demonstrate that eps15 is member of a gene family that is highly conserved during evolution. An essential function of eps15 in cell growth regulation is underscored by our observation of ubiquitous expression at the transcript and the protein level in normal and malignant human cells. The human EPS15 locus maps to chromosome 1p31-p32, a region involved in deletion in neuroblastoma, translocations in acute lymphoblastic leukemia, and exhibiting a fragile site.
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PMID:The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32. 818 52

Neurotransmitter receptors alter membrane excitability and synaptic efficacy by generating intracellular signals that ultimately change the properties of ion channels. Through expression studies in Xenopus oocytes and mammalian cells, we found that the G protein-coupled m1 muscarinic acetylcholine receptor potently suppresses a cloned delayed rectifier K+ channel through a pathway involving phospholipase C activation and direct tyrosine phosphorylation of the K+ channel. Furthermore, analysis of neuroblastoma cells revealed that a similar tyrosine kinase-dependent pathway links endogenous G protein-coupled receptors to suppression of the native RAK channel. These results suggest a novel mechanism by which neurotransmitters and hormones may regulate a specific type of K+ channel that is widely expressed in the mammalian brain and heart.
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PMID:Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor. 826 14

There is considerable interest in the role of the TRK family of neuotrophin receptors in regulating growth and differentiation in normal and neoplastic nerve cells. A neuroblastoma is a common pediatric tumor derived from the neural crest, and the majority of favorable neuroblastomas express a high level of TRK-A mRNA. However, little is known about the expression or function of TRK-B in these tumors. TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the N-myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both TRK-B and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B as well as phosphorylation of phospholipase C-gamma 1, the extracellular signal-regulated kinases 1 and 2, and phosphatidylinositol-3 kinase. BDNF also induces expression of the immediate-early genes c-FOS and NGFI-A but not NGFI-B or NGFI-C. In addition, BDNF appears to promote cell survival and neurite outgrowth. SMS-KCN cells also express TRK-A, which is phosphorylated in response to nerve growth factor. However, the downstream TRK-A signaling is apparently defective. Finally, we determined that in a series of 74 primary neuroblastomas, 36% express TRK-B mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be preferentially expressed in more-differentiated tumors (ganglioneuromas and ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively in immature neuroblastomas with N-myc amplification. Our findings suggest that in TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be particularly important for growth and differentiation of neuroblastomas with N-myc amplification.
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PMID:Expression and function of TRK-B and BDNF in human neuroblastomas. 826 43

Platelet-activating factor (PAF) elicited an increase in intracellular Ca2+ concentration, [Ca2+]i, in neuroblastoma x glioma hybrid NG 108-15 cells as measured by fura-2 fluorescence method. The rise in [Ca2+]i was primarily due to the influx of Ca2+ from extracellular source. Preincubation of cells with the Ca(2+)-ion channel blockers, including verapamil, nifedipine and conotoxin, did not affect the Ca(2+)-response stimulated by PAF, indicating that the PAF-elicited Ca(2+)-influx is not mediated through the classical voltage-dependent Ca(2+)-ion channels. In contrast, SK&F 96365, which is an inhibitor of receptor-operated calcium channel, blocked the PAF-elicited Ca(2+)-response dose-dependently. When cells were pretreated with the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), PAF-elicited Ca(2+)-signal was diminished substantially. In contrast, the protein kinase A activator, forskolin, has no effect on the Ca(2+)-response induced by PAF. Further experiment demonstrated that genistein, an inhibitor of tyrosine kinase, also caused inhibition on PAF-induced Ca(2+)-response significantly. There results suggest that the PAF receptor-coupled Ca(2+)-ion channel is subjected to the modulation by protein kinase C and tyrosine-specific kinase. Pretreatment of cells with PAF resulted in the desensitization of the Ca(2+)-response following further stimulation with the same agonist. The heterologous desensitization of the PAF-induced Ca2+ influx was also observed in cells pretreated with bradykinin or to a less extent with ATP. Conversely, pretreatment of cells with PAF affected only partially the Ca(2+)-response elicited by bradykinin or ATP. Additive response was observed when PAF and ATP were added together but not PAF and bradykinin.
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PMID:Platelet-activating factor receptor-mediated calcium influx in NG 108-15 cells. 827 98

Two alternatively spliced mouse lymphocyte and brain ltk cDNAs predict small transmembrane tyrosine kinases that use CUG translational start codons and that differ upstream of their transmembrane segment. A recently isolated human neuroblastoma ltk cDNA, in contrast, includes a regular AUG start codon and predicts a more conventional receptor kinase with a larger N-terminal segment. This raised the suggestion that previous mouse cDNAs may have been aberrantly spliced or incomplete and questioned the significance of a recent study that localized the lymphoid ltk protein to the endoplasmic reticulum. Here we show that mice tissue-specifically express four ltk mRNAs. In addition to the two previously described lymphoid and brain mRNAs, we now describe two mRNAs from C1300 neuroblastoma cells that start with five exons which are absent from lymphoid or brain transcripts. The pair of C1300 mRNAs differ by the same alternatively spliced exon that distinguishes brain from lymphoid mRNAs and predict much larger receptor-type kinases that use regular AUG start codons. Our results also show that at least one of the larger, more conventional C1300 ltk receptors shares the endoplasmic reticulum localization of the shorter lymphoid protein.
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PMID:Four tissue-specific mouse ltk mRNAs predict tyrosine kinases that differ upstream of their transmembrane segment. 838 Sep 20

In differentiated SH-SY5Y human neuroblastoma cells, various opioids exhibited a wide range of potencies (Ki) in acutely inhibiting adenylate cyclase to different extents (Imax). After exposure of the cells to opioids for 24 hr, the initially reduced cAMP content of the cells recovered toward pre-exposure levels. Withdrawal of agonist from, or addition of antagonist to, the tolerant cells rapidly increased the cAMP content to 1.5 times the basal value. Long term treatment of the cells with agonists of high acute potency, such as Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and levorphanol, decreased the Bmax of the antagonist [3H]naltrexone by 80-95%, increased the Ks for GTPase stimulation 10-14-fold, and increased the Ki for adenylate cyclase inhibition 2-3-fold. On the other hand, these parameters were only marginally affected by agonists of lower acute potency, such as profadol and morphiceptin, regardless of their Imax in inhibiting adenylate cyclase. The reduction in the level of receptor binding was experimentally not dissociable from effector desensitization. Tyr-D-Ala-Gly-(Me)Phe-Gly-ol retained the characteristics of a potent agonist in inducing tolerance even under conditions of submaximal signal, produced by lower concentrations of the peptide or by pretreatment with pertussis toxin. Alkylation of receptors by beta-chlornaltrexamine, although it reduced [3H]naltrexone binding by 50%, did not significantly alter the rank order of opioid agonists based on their ability to acutely inhibit adenylate cyclase. These results show that in opioid-tolerant SH-SY5Y cells the concurrently occurring down-regulation of receptor and shifts in the concentration dependence of effector response correlate with the potency of a given opioid in producing its acute effect but not with the maximum extent of that effect.
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PMID:Receptor mechanisms of opioid tolerance in SH-SY5Y human neural cells. 838 4


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