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

Human neuroblastoma cells (clone SHSY-5Y) induced to differentiate by 12-O-tetradecanoylphorbol-13-acetate (TPA) are shown to possess properties characteristic of mature ganglion cells. Elevation of the external K+ concentration, exposure to Ca2+ ionophore A23187, and acetylcholine all stimulate the release of preloaded 3H-noradrenaline in the presence but not in the absence of added Ca2+. Acetylcholine causes a fall in the 86Rb+ or 14C-TPMP equilibrium potential across the plasma membrane and stimulates 86Rb+ efflux. These responses are prevented by atropine. Acetylcholine and muscarine but not nicotine stimulate an increase in 45Ca2+ influx, an effect blocked by atropine. None of these responses have been observed in nondifferentiating cells. Muscarinic receptors, however, as measured by the binding of tritiated quinuclidinyl benzilate (3H-QNB), were present to a similar extent in control and differentiated cells. Both cell types also exhibit an accelerated release of Ca2+ in response to acetylcholine, but the control cells were at least 1 order of magnitude more sensitive to the agonist.
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PMID:Development of a neural phenotype in differentiating ganglion cell-derived human neuroblastoma cells. 309 56

Four monoclonal antibodies were obtained to rat brain choline acetyltransferase (CAT). The enzyme was purified 95,000-fold from rat brain by precipitation with acetic acid at pH 4.5, fractionation with 40 to 60% (NH4)2SO4, CM-Sephadex chromatography, and affinity column chromatography on agarose-hexane-coenzyme A. The enzyme preparation was applied to the affinity column in the presence of 10 mM acetylcholine to increase the affinity of CAT for coenzyme A; the enzyme then was eluted with 10 mM acetyl coenzyme A. Fusion of P3X63 Ag8 myeloma cells with spleen cells isolated from a BALB/c mouse that had been immunized with affinity-purified CAT with a specific activity of 29.4 mumol of ACh synthesized/min/mg of protein resulted in the isolation of four hybridomas synthesizing antibodies to CAT that inhibit the activity of the enzyme. Anti-CAT 1 or 2 inhibits CAT activity 100%. At the highest antibody concentration tested, anti-CAT 3 inhibited acetylcholine synthesis 80%. Hybridoma antibody-dependent inhibition of CAT activity was reversed by dissociation of immune complexes via dilution, demonstrating that antibody binding does not irreversibly alter the structure of the enzyme. When bound to [rabbit anti-mouse IgG . protein A Staphylococcus aureus] complexes, anti-CAT 1, 3, and 4 each were effective reagents for the precipitation of CAT activity from solution. Thirty-one to 53% of the precipitated enzyme was recovered following the dissociation of immune complexes. Anti-CAT 1, 2, and 3 inhibit CAT from 18-day chick embryo brain, NS20-Y mouse neuroblastoma cells, and rat brain.
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PMID:Inhibition of choline acetyltransferase by monoclonal antibodies. 388 Aug 11

Benzodiazepines have been shown to change the turnover rate of 5-HT, ACh and catecholamines stored in selected brain areas, but the doses required for these effects are several-fold higher than those which elicit a persistent punished behavior or antagonize isoniazid, bicuculline or picrotoxin convulsion. The selective antagonism against convulsions elicited by drugs that impair GABAergic transmission, the capability of muscimol and other GABA receptors agonists to mimic behavioral and anticonvulsant action of the benzodiazepines have suggested that benzodiazepines facilitate GABA transmission. This facilitation of the GABA tranmission is due to an allosteric facilitation of high-affinity GABA binding to postsynaptic receptors. Also, the high-affinity binding of the benzodiazepines can be facilitated by GABA mimetics. Endogenous inhibitors of the benzodiazepines and GABA binding extracted from synaptic membranes play a role in facilitating these interactions. Using neuroblastoma 2A cells as a model and Cl- influx as an index of GABA receptor activation, it will be shown that the benzodiazepines facilitates not only GABA binding but also its action on Cl- channels. Also, glioma C6 cells have high affinity receptors for GABA and benzodiazepine binding but these binding sites are not linked to a Cl- channel. It is concluded that the benzodiazepines displace a regulatory protein for high-affinity GABA receptors and thereby facilitate GABAergic transmission.
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PMID:Benzodiazepines and neurotransmitters. 610 85

The neuroblastoma x glioma hybrid clone NG108-15 is able to release acetylcholine upon depolarization and form cholinergic neuromuscular synapses in culture. Normal functioning of cholinergic synapses is thought to be dependent on the ability of a neuron to take up extracellular choline, since neurons are unable to synthesize choline de novo. For these two reasons it became important to characterize the choline uptake system of NG108-15 cells. The uptake system appears to bear little if any resemblance to the Na+-dependent high-affinity choline uptake system normally associated with cholinergic neurons. Although the cells appear to possess both high- and low-affinity choline uptake systems, neither system is dependent on Na+ and uptake actually is increased about 60% by the substitution of sucrose for NaCl. Acetylcholine synthesis also is not dependent on Na+, since sucrose, substituted for NaCl, also stimulates acetylcholine synthesis. Changes in the concentrations of the other ions in the uptake medium have little effect on uptake, with the exception that elevated Ca2+ or Mg2+ reverses the stimulation of choline uptake produced by substitution of sucrose for NaCl. Choline uptake is inhibited by hemicholinium-3, but only at high concentrations of the drug (IC50 = 30-80 microM). The metabolic poisons cyanide and iodoacetate inhibit uptake by only 30-40%. Growth of the cells in N6,O2' dibutyryladenosine-3',5'-cyclic monophosphate, which promotes functional and morphological differentiation of the cells, decreased slightly the total amount of choline taken up but had no additional effect on the uptake system. Thus, it appears that NG108-15 cells are capable of forming functional cholinergic synapses with muscle cells even though the neuroblastoma does not possess the high-affinity choline uptake system normally associated with cholinergic neurons.
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PMID:Choline uptake by the neuroblastoma x glioma hybrid, NG108-15. 625 99

Cholinergic murine neuroblastoma cells, maintained in vitro, were exposed to a low concentration (0.4 micrograms/ml) of adriamycin. Morphologically the treated cells appeared to differentiate. The cell bodies increased in size from an average fixed cell body diameter of 7-13 to 25-40 micrometers, the cells developed long processes, became argyrophilic and the percentage of cells undergoing mitosis decreased relative to controls. Acetylcholine esterase activity increased in the drug-treated cells suggesting induction of differentiation. However, choline acetyltransferase activity and ganglioside composition remained unchanged. In addition, inoculation of mice with 2 x 10(5) viable drug-treated or control cells resulted in all of the mice developing neuroblastoma. No differences were observed in either the rate of tumor development or survival times. These results suggest that neuroblastoma cells may survive adriamycin treatment by becoming 'differentiated', ceasing cell division until conditions favor their undergoing another cell cycle.
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PMID:Biochemical and morphological study of adriamycin-induced changes in murine neuroblastoma cells. 707 39

A factor or factors released by cultured NG108-15 neuroblastoma X glioma hybrid cells and added to the medium of rat myotube primary cultures was found to immobilize some of the previously mobile acetylcholine receptors in the myotube membrane. Partial receptor immobilization occurred within 3 h after the beginning of treatment with the NG108-15-conditioned medium factor and persisted for at least 24 h of continuous treatment. A similarly derived conditioned medium concentrate from the non-neuronal parent glioma cell line did not immobilize receptors, relative to untreated controls. Acetylcholine receptors were visualized by fluorescent alpha-bungarotoxin and their lateral motion was observed by the technique of fluorescence photobleaching recovery.
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PMID:A factor from neurons induces partial immobilization of nonclustered acetylcholine receptors on cultured muscle cells. 720 2

Pharmacological characteristics of native neuronal nicotinic acetylcholine receptor-mediated ion currents in mouse N1E-115 neuroblastoma cells have been investigated by superfusion of voltage clamped cells with known concentrations of the agonists acetylcholine, nicotine and cytisine, and the antagonists alpha-bungarotoxin and neuronal bungarotoxin. The sensitivity of the nicotinic acetylcholine receptor for agonists followed the agonist potency rank-order: nicotine approximately acetylcholine >> cytisine. The EC50 values of acetylcholine and nicotine are 78 microM and 76 microM, respectively. Equal concentrations of acetylcholine and nicotine induce inward currents with approximately the same peak amplitude whereas cytisine induces much smaller inward currents. Acetylcholine-induced currents are unaffected by high concentrations of alpha-bungarotoxin. Conversely, at 10 and 90 nM neuronal bungarotoxin reduces the amplitude of the 1 mM acetylcholine-induced inward current to 47% and 11% of control values, respectively. Both the agonist potency rank-order and the differential sensitivity to snake toxins of nicotinic receptors in N1E-115 cells are consistent with the known pharmacological profile of alpha 4 beta 2 nicotinic receptors expressed in Xenopus oocytes and distinct from those of all other nicotinic acetylcholine receptors of known functional subunit compositions. All data indicate that the native nicotinic acetylcholine receptor in N1E-115 cells is an assembly of alpha 4 and beta 2 subunits, the putative major subtype of nicotinic acetylcholine receptor in the brain.
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PMID:alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells. 752 90

1. Pb2+ affects neuronal nicotinic acetylcholine receptors (nAChR) in N1E-115 neuroblastoma cells in a dual manner. At nanomolar concentrations a blockade is observed, while at submillimolar concentrations this blocking effect is reversed. 2. The Xenopus oocyte expression system was used to examine whether the dual effect of Pb2+ is related to a differential action on nAChR subtypes. Effects of Pb2+ were investigated in oocytes expressing nAChR after co-injection of alpha 3 and beta 2 or alpha 3 and beta 4 cDNA. 3. At 1-250 mumol/L, Pb2+ causes a 10-1000% increase of the response mediated by the alpha 3 beta 2 nAChR. 4. Pb2+ blocks ACh-induced inward currents mediated by alpha 3 beta 4 nAChR. The inhibitory potency of Pb2+ greatly varies between cells. In 50% of the cells concentrations < or = 1 mumol/L Pb2+ blocked the nicotinic response by 31-93%. In the other cells even at higher concentrations Pb2+ caused only 0-65% inhibition. 5. These results show that Pb2+ may both potentiate and block nAChR, depending on the type of nAChR subunit expressed.
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PMID:Subunit-dependent action of lead on neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. 755 31

Muscarinic acetylcholine receptor (mAChR) subtype (m1-m4)-specific cDNAs were transfected into NL308 neuroblastoma-fibroblast hybrid cells and clones expressing each of the individual mAChR subtypes m1, m2, m3 and m4 obtained. Acetylcholine increased phosphoinositide (PI) turnover in m1- and m3-transformed cells, but did not produce detectable changes in m2- and m4-transformed cells. In cells expressing m1 and m3 subtypes, ACh produced an initial outward K+ current, followed by a cationic current. In cells expressing m2 and m4 receptors, only the initial K+ current was detected. The outward currents were associated with a rise in intracellular Ca2+ as measured with Fura-2 or Indo-1, and were inhibited by chelating intracellular Ca2+ with external BAPTA-AM, or by external charybdotoxin or Ba2+: hence they were attributed to the activation of a Ca(2+)-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-1 Pertussis toxin (PTX), whereas that in m1- and m3-transformed cells was not. These results suggest that m2- and m4-receptors in transformed NL308 cells coupled to PTX-sensitive G-protein which is capable of mobilizing intracellular Ca2+ and activate IK(Ca), whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.
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PMID:Coupling of m2 and m4 muscarinic acetylcholine receptor subtypes to Ca(2+)-dependent K+ channels in transformed NL308 neuroblastoma x fibroblast hybrid cells. 809 28

The incorporation of [3H]serine into lipids, water-soluble metabolites and proteins by the human neuroblastoma cell line LA-N-1 exposed to oxotremorine-M, a muscarinic agonist, was investigated. Oxotremorine-M increased the incorporation of this labelled precursor into phosphatidylserine and proteins in a concentration-dependent manner, with the maximal stimulation at 250 microM. This activation was blunted by 100 microM atropine. There were no detectable changes of the radioactivity in the water-soluble metabolites. Acetylcholine, another muscarinic agonist, slightly decreased the serine incorporation into lipids, but did not affect the protein or water-soluble compartments. Several other muscarinic agonists, including 250 microM pilocarpine, 100 microM McN-A-343 and 1 mM carbachol, did not effect these [3H]serine incorporations. Preincubation of cells with 1 mM oxotremorine M, or 1 mM carbachol, or 1 mM McN-A-343, for 4 h prevented the oxotremorine-M-induced increase of serine incorporation. These observations are consistent with the oxotremorine-M action being mediated by muscarinic-receptor occupancy. The G-protein inhibitor guanosine 5'-[beta-thio]diphosphate (1 mM) and the G-protein activators, guanosine 5'-[gamma-thio]triphosphate (100 microM) and A1F3, prevented the oxotremorine stimulation. The muscarinic agonists, 250 microM oxotremorine-M, 1 mM carbamoylcholine and 500 microM acetylcholine, triggered the accumulation of inositol mono- and di-phosphates by cells that had been prelabelled with myo-[3H]inositol, and this phospholipase C activation was blunted by 100 microM atropine. The protein kinase C inhibitor H7 prevented the oxotremorine-M stimulation of serine incorporation. Over-night exposure of LA-N-1 cells to 100 nM phorbol 12-myristate 13-acetate resulted in a decrease of cytosolic protein kinase C activity, and prevented the oxotremorine-M stimulation of serine incorporation. Neither oxotremorine-M nor acetylcholine caused a redistribution of protein kinase C activity between the cytosol and membrane compartments. In addition, oxotremorine-M did not activate phospholipase D of the LA-N-1 cells.
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PMID:Modulation of phosphatidylserine synthesis by a muscarinic receptor occupancy in human neuroblastoma cell line LA-N-1. 817 97


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