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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Muscarinic receptors in N1E 115 mouse neuroblastoma cells were characterized by competition binding experiments using three agonists and five antagonists, including 4-DAMP and AF-DX 116, and by studying the effect of agonist stimulation on the cellular cAMP and cGMP content. The results of the binding studies with the antagonists suggest that only one single homogeneous binding site of the M1 muscarinic receptor subtype is present. For the binding with the agonists, two binding sites were detected, one with high affinity for the ligand (between 53 and 77% of the total binding sites depending on the agonist) and one with low affinity. In contrast to the results obtained with the binding experiments using antagonists, the study of the cellular cyclic nucleotide response upon carbachol stimulation suggested the presence of both the M1 and M2 subtypes as there was an increase in cyclic GMP concentration while at the same time, the prostaglandin-stimulated synthesis of cyclic AMP was inhibited. Considering both binding and functional data we suggest that in N1E 115 cells a majority of M1 and a minority of M2 muscarinic receptors are present; there is no evidence for the presence of M3 muscarinic receptors.
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PMID:Study of the muscarinic receptor subtypes in N1E 115 mouse neuroblastoma cells. 164 47

The morphological change of several neuroblastoma cell lines induced by griseolic acid, a novel and potent inhibitor of cyclic nucleotide phosphodiesterase (PDE), was examined. In the cell lines tested, Neuro-2a (a murine neuroblastoma cell line) showed dose-dependent (1 microM-1 mM) neurite extension. Griseolic acid markedly increased the intracellular cyclic AMP level of Neuro-2a cells, suppressed DNA synthesis (82% at 1 mM), and induced multipolar (multiple-neurite-bearing)-type neuritogenesis. A similar type of neurite outgrowth was induced by 8-bromo-cyclic AMP, which also elevated the intracellular cyclic AMP concentration. In contrast, when Neuro-2a cells were treated with retinoic acid, neurite formation was of the monopolar (single-neurite-bearing) type. Papaverine and theophylline, which have been frequently used as PDE inhibitors, failed to induce these morphological changes up to 1 mM, probably owing to the lesser potency of these compounds as compared with griseolic acid on the inhibition of PDE. Retinoic acid, theophylline, and papaverine were ineffective at elevating the intracellular cyclic AMP level. These results suggest that multipolar-type cell shape change in Neuro-2a cells is correlated with the accumulation of intracellular cyclic AMP and that griseolic acid is a useful compound to induce neuroblastoma cells into terminal differentiation.
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PMID:Multiple neurite formation in neuroblastoma cell lines by griseolic acid, a potent inhibitor of cyclic nucleotide phosphodiesterases. 164 54

The effects of the lithium ion (Li+) on receptor-mediated synthesis of second messengers were determined, when cellular sodium channels were quiescent or excited, using the murine neuroblastoma clone (N1E-115). In this clone, lithium inhibited the receptor-mediated synthesis of cyclic AMP and cyclic GMP and it also increased the accumulation of inositol phosphates by a receptor-mediated process. When veratridine (20 microM) excited the sodium channel, the effects of lithium were potentiated. However, tetrodotoxin, a sodium channel blocker, completely prevented this potentiation. These results suggest that when neurons are depolarizing actively and intraneuronal levels of lithium increase by entry through the sodium channel, lithium has a more potent intracellular effect. As a result, lithium would have more potent and selective effects in those pathologically-active neurons underlying manic-depressive disorder.
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PMID:Potentiation by a sodium channel activator of effects of lithium ion on cyclic AMP, cyclic GMP and inositol phosphates. 165 Sep 29

Quinacrine altered the equilibrium binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to the muscarinic receptor in membranes from N18TG2 neuroblastoma cells. At 1 microM quinacrine, the apparent Kd for [3H]QNB binding was shifted from 48 to 210 pM without a decrease in the maximum binding. The competition binding profile of quinacrine indicates that it displaced [3H]QNB binding with an IC50 of 460 nM in a manner consistent with competitive inhibition. Quinacrine blocked the muscarinic inhibition of cyclic AMP accumulation by carbachol in cultured N18TG2 neuroblastoma cells without affecting arachidonic acid release or Gi coupling to the adenylate cyclase. The disruption of muscarinic receptor function by quinacrine may provide an explanation for its blockade of the muscarinic response in cells.
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PMID:Muscarinic receptor binding is inhibited by quinacrine. 165 14

Mouse neuroblastoma x rat glioma hybrid cells (N x G, 108CC15) were used to study the inhibitory effects of the synthetic opioid D-Ala2-D-Leu5-enkephalin (DADLE), somatostatin, adrenaline-alpha 2 and angiotensin II on voltage-dependent Ca(2+)-currents (ICa) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N x G cells with pertussis toxin or intracellular infusion of GDP beta S indicating an involvement of a pertussis toxin sensitive GTP-binding protein (G-protein), presumably Go. The effect of DADLE, the strongest inhibitor of ICa, was studied during dibutyryl cyclic AMP (dBcAMP) induced differentiation. Using omega-conotoxin GVIA (omega-CTX) and methoxyverapamil (D600) as specific Ca(2+)-channel blockers of the N- and L-type Ca(2+)-channels, it was found that in N x G cells DADLE predominantly induces inhibition of T- and N-type Ca(2+)-channels.
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PMID:Inhibitory modulation of fast and slow Ca(2+)-currents in neuroblastoma x glioma cells during differentiation. 165 35

Muscarinic receptor-linked Ca2+ mobilization and changes in cyclic AMP were studied in SH-SY5Y and IMR 32 human neuroblastoma cell lines. Muscarinic agonists acetylcholine, carbachol, methacholine and muscarine induced an increase in cytosolic free Ca2+ in a pertussis toxin (100 ng/ml)-insensitive manner in both cell lines. The ED50 values in IMR 32 cells (8-98 microM) were one order of magnitude higher than in SH-SY5Y cells (0.3-1.6 microM). Oxotremorine and pilocarpine failed to mobilize Ca2+ in IMR 32 cells. Pirenzepine antagonized carbachol-induced Ca2+ mobilization in SH-SY5Y cells with a Ki value in the range of 150-189 nM whereas the corresponding values in IMR 32 cells were 24-28 nM. Atropine inhibited a carbachol-stimulated increase in cytosolic Ca2+ with an equal potency in both cell lines (Ki 2-3 nM). Carbachol stimulated cyclic AMP (cAMP) accumulation in SH-SY5Y cells in a pertussis toxin-insensitive manner. In IMR 32 cells carbachol inhibited prostaglandin E1-stimulated cAMP accumulation. Treatment of IMR 32 cells with pertussis toxin abolished the inhibition of stimulated cAMP accumulation. These results suggest that in SH-SY5Y cells the M3 muscarinic receptor couples to both Ca2+ mobilization and stimulation of cAMP accumulation. In IMR 32 cells the M1 receptor seems to couple to Ca2+ mobilization whereas the inhibition of stimulated cAMP accumulation is coupled to a non-M1 subtype by an inhibitory G-protein.
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PMID:Differential coupling of muscarinic receptors to Ca2+ mobilization and cyclic AMP in SH-SY5Y and IMR 32 neuroblastoma cells. 165 23

Cultured human neuroblastoma (GOTO) cells were induced to differentiate by dibutyryl cyclic AMP (Bt2cAMP) and/or retinoic acid (RA). A combination of Bt2cAMP (1 mM) and RA (1 microM) yielded the most significant networks of neurites after 3 to 4 days, this being associated with the reduction of N-myc mRNA levels. Next, we examined several cellular genes that were possibly linked with changes in N-myc gene expression under these conditions. Among the genes examined, both nucleolin and a major heat-shock protein (hsp70) mRNAs showed changes concomitant with those in N-myc mRNA levels when induced by Bt2cAMP and RA. Dibutyryl cAMP alone induced several short cellular processes and caused a marked decrease in N-myc mRNA within 2 days. RA alone induced a few long and straight neurites along the longitudinal axis of individual cells and a significant decrease in growth rate but showed neither network formation nor a decrease in N-myc gene expression. These results indicate differential effects of Bt2cAMP and RA on the regulatory mechanisms of both cell proliferation and differentiation and also indicate a possible association of expression of N-myc gene with those of hsp70 and nucleolin genes.
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PMID:Down modulation of N-myc, heat-shock protein 70, and nucleolin during the differentiation of human neuroblastoma cells. 165 99

Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate formation, peaking at 20 s. There was more than a 10-fold difference between the ED50 for PGE1 at cyclic AMP formation (70 nM) and its ED50 values at IP accumulation (1 microM), cyclic GMP formation (2 microM), and [Ca2+]i increase (5 microM). PGE1-mediated IP accumulation, cyclic GMP formation, and [Ca2+]i increase depended on both the concentration of PGE1 and extracellular calcium ions. PGE1 had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE2, PGF2 alpha, or PGD2. A protein kinase C activator, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, had opposite effects on PGE1-mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). These data suggest that there may be subtypes of the PGE1 receptor in this clone: a high-affinity receptor mediating cyclic AMP formation, and a low-affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization.
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PMID:Two possibly distinct prostaglandin E1 receptors in N1E-115 clone: one mediating inositol trisphosphate formation, cyclic GMP formation, and intracellular calcium mobilization and the other mediating cyclic AMP formation. 165 30

1. N1E-115 mouse neuroblastoma cells morphologically differentiate by extending neurites in a period of seven days after addition of 2% DMSO to the culture medium. We used the whole-cell patch clamp technique to measure calcium currents in these cells under conditions where voltage clamp of the whole membrane was assured. 2. Current densities of both T and L type calcium currents were identical in cells included to differentiate with dibutyryl cyclic AMP and cells induced to differentiate with dimethylsulphoxide (DMSO). Cells differentiated with DMSO were used for all subsequent experiments. 3. All morphologically differentiated cells showed a T type calcium current. In contrast, a minority of morphologically undifferentiated cells did not show a T current. 4. Once expressed, both T and L currents did not change either in current density or in behaviour over a period of five days. 5. These data demonstrate that expression of a T current always precedes neurite extension, and suggest a role for calcium currents in triggering morphological differentiation.
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PMID:Expression of T-type calcium current precedes neurite extension in neuroblastoma cells. 166 78

NEURO-2A neuroblastoma cells were differentiated by the addition of dibutyryl-cyclic AMP, resulting in an increase in transcription of mRNA coding for the two neurofilament polypeptides NF-L and NF-M. The mRNAs for these two polypeptides appeared to be co-expressed with both being switched on at 24 h after the addition of drug. This was in contrast to NF-H whose induction was only seen at 60 h following addition of drug. These results are in good agreement with the expression time course previously reported in-vivo and suggest that the neurofilament triplet polypeptides can be divided into two subsets which appear to be under different genetic control mechanisms according to their time course of expression.
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PMID:Temporal expression of neurofilament polypeptides in differentiating neuroblastoma cells. 166 92


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