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)

SK-N-SH and SH-SY5Y human neuroblastoma cells treated by 12-)-tetradecanoyl-phorbol-13-acetate(TPA) express morphological and biochemical changes, which indicate that differentiation towards more mature cells has occurred. The most prominent morphological changes were the development in 40-60% of the cells of cell-surface projections longer than 50 micrometers and cytoplasmic neurosecretory granules demonstrated by electron microscopy. At the biochemical level, TPA induced a two-fold increase in the relative activity of neuron-specific enolase and 30- to 40-fold increase in noradrenaline and adrenaline concentrations. A decrease in proliferation rate of TPA-treated cells was observed. The biological effects of TPA were slightly potentiated by nerve growth factor.
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PMID:Phenotypic changes of human neuroblastoma cells in culture induced by 12-O-tetradecanoyl-phorbol-13-acetate. 730 95

The daily time course of urinary catecholamine excretion was determined for hyperactivity of the sympathoadrenal system (3 phaeochromocytomas, 1 neuroblastoma), disturbed adrenal function (M. Addison and partial adrenal insufficiency), bilateral adrenalectomy (one patient), in 8 healthy patients receiving dexamethasone, and in a control group. All groups showed a circadian rhythm of catecholamine excretion. In the patients with phaeochromocytoma, the excretion of catecholamines and vanilmandelic acid showed a shift of phase compared with the control group. In patients with hyperfunction of the sympathoadrenal system, catecholamines and vanilmandelic acid fluctuated with similar amplitudes, whereas in healthy patients vanilmandelic acid and dopamine showed much smaller fluctuations of concentration than adrenaline and noradrenaline.
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PMID:[Circadian rhythm of free catecholamine excretion in disturbed adrenal function (author's transl)]. 732 94

We describe a child with a localised pelvic neuroblastoma and a hypertensive crisis during the first weeks of life due to elevated systemic norepinephrine of tumoural origin. In spite of treatment with high doses of alpha-blockers, blood pressure did not respond fully and the boy had a very unstable circulation. Surgery was performed at one month of age. Adenosine, a potent short-acting vasodilator, was used for peroperative blood pressure control to protect the patient from an uncontrolled hypertensive crisis. During tumour manipulation the child became hypertensive with systolic pressure exceeding 130 mm Hg and adenosine infusion (100 micrograms.kg-1.min-1) was started with a prompt normalisation of the blood pressure. Adenosine infusion could be discontinued after tumour removal. Norepinephrine, dopamine, homovanillic acid and vanillylmandelic acid in urine were elevated preoperatively and normalised at follow up. Plasma concentrations of norepinephrine and dopamine were elevated preoperatively. Norepinephrine increased during hypertension due to tumour manipulation. Plasma neuropeptide Y increased during tumour manipulation but still within the normal range for infants. It is concluded that adenosine can be used peroperatively in children with severe hypertension and in this case no adverse effects of adenosine were noted. Furthermore, tumour synthesis and systemic release of norepinephrine, but not neuropeptide Y, contributed to hypertension in this child with neuroblastoma.
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PMID:Adenosine for per-operative blood pressure control in an infant with neuroblastoma. 757 24

[131I]metaiodobenzylguanidine ([131I]MIBG) is selectively taken up and stored by tumours derived from the neural crest, and is used for diagnosis and treatment of neuroblastoma (NB). The antitumoral effect of [131I]MIBG is closely related to the intracellular level of the radiopharmaceutical compound, which is dependent on uptake and storage/release mechanisms. While MIBG uptake is well characterised, storage and release mechanisms are still controversial. In order to better characterise [125I]MIBG release mechanisms, we studied the basal and stimulated efflux of [125I]MIBG in the human NB cell line, SH-SY5Y, preloaded with 0.1 microM [125I]MIBG for 1 h. We found that [125I]MIBG basal efflux is highly temperature-dependent, that [125I]MIBG release, induced by cell depolarisation with high potassium, is mainly calcium-independent, and induced by exchange with cold MIBG or noradrenaline, inversion of the sodium gradient across the cell membrane by veratridine by substitution of sodium chloride with equimolar concentration of lithium chloride. The exposure of NB cells to imipramine, an Uptake-1 inhibitor, also produces a net stimulatory effect on [125I]MIBG release. However, when used in association with other releasing stimuli, such as higher levels of intracellular sodium or external agonists, imipramine abolishes the consequent increase of [125I]MIBG release. Our findings suggest that stimulated [125I]MIBG release is mediated by a carrier, most probably the uptake carrier working in a reverse mode, while a minimal fraction of [125I]MIBG is released by an exocytotic mechanism.
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PMID:Release mechanisms of [125I]meta-iodobenzylguanidine in neuroblastoma cells: evidence of a carrier-mediated efflux. 757 75

Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.
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PMID:Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression. 757 74

Dimethylphenylpiperazinium iodide (a nicotinic agonist) evokes noradrenaline release from human neuroblastoma SH-SY5Y cells that have been pretreated with 12-O-tetradecanoylphorbol 13-acetate for 8 min. This effect of dimethylphenylpiperazinium iodide was inhibited by 1 microM mecamylamine but not by 1 microM atropine, which suggests that SH-SY5Y cells express nicotinic receptors coupled to the release of noradrenaline. Dimethylphenylpiperazinium iodide-evoked release was enhanced by 5 microM Bay K 8644 (an L-type calcium agonist) and inhibited by 1 microM nifedipine. Dimethylphenylpiperazinium iodide depolarised SH-SY5Y cells and enhanced the level of intracellular calcium in cells loaded with fura 2. The effects of dimethylphenylpiperazinium iodide on noradrenaline release, depolarisation, and intracellular calcium levels were all inhibited by 1 microM desmethylimipramine. The results of this study show that nicotinic receptors in SH-SY5Y cells stimulate noradrenaline release by activation of L-type calcium channels.
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PMID:Nicotinic receptor-mediated release of noradrenaline in the human neuroblastoma SH-SY5Y. 768 69

Activation of the G-protein-coupled muscarinic (M3) receptor in human neuroblastoma SH-SY5Y cells is known to lead to phosphoinositol hydrolysis and noradrenaline release. In this study, the effect of carbachol on tyrosine phosphorylation and mitogen-activated protein (MAP) kinase activity in SH-SY5Y cells was examined. Carbachol concentration-dependently induced tyrosine phosphorylation of several proteins, including one of 42 kDa. This tyrosine-phosphorylated 42 kDa protein co-eluted from a Mono Q anion-exchange column with MAP kinase activity and with immunologically detected MAP kinase. Stimulation of tyrosine phosphorylation and activation of MAP kinase were also observed after incubation of cells with phorbol 12-myristate 13-acetate (PMA) and epidermal growth factor (EGF). Down-regulation or inhibition of protein kinase C (PKC) abolished the stimulatory effects of both carbachol and PMA on MAP kinase activity, whereas EGF-stimulated MAP kinase activity remained unaffected. Thus carbachol acting through the muscarinic (M3) receptor PKC-dependently induced tyrosine phosphorylation and activation of a 42 kDa MAP kinase in SH-SY5Y cells, whereas EGF-induced MAP kinase activation occurred independently of PKC.
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PMID:Stimulation of tyrosine phosphorylation and mitogen-activated-protein (MAP) kinase activity in human SH-SY5Y neuroblastoma cells by carbachol. 769 May 47

This paper describes the establishment of a new polyclonal human neuroblastoma cell line NAL-GT. Pharmacological characterisation of a cell line comprising > 70% neurones using radioligand binding, Ins(1,4,5)trisphosphate (Ins(1,4,5)P3) mass formation, intracellular Ca2+ ([Ca2+]i) determinations and cyclic adenosine monophosphate (cAMP) formation has been performed. Carbachol (1 mM) and noradrenaline (10 microM) increased Ins(1,4,5)P3 formation 2-3-fold basal. Noradrenaline (10 microM) and morphine (10 microM) reduced forskolin stimulated cAMP formation by 19.7 and 30.5%, respectively. Carbachol (1 mM) and K+ (50 mM) increased [Ca2+]i. These data indicate that polyclonal (heterogeneous) NAL-GT cells express muscarinic, alpha 1 and alpha 2 adrenoceptors, opioid receptors and voltage-sensitive Ca2+ channels and may prove useful in the study of the cellular basis of drug action.
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PMID:Characterisation of a new human neuroblastoma cell line, NAL-GT. 774 83

1. Human neuroblastoma (SH-SY5Y) cells were preincubated with [3H]-noradrenaline ([3H]-NA) in the presence of 0.2 mM pargyline to examine the modulation of K(+)-evoked [3H]-NA release by muscarinic agonists. 2. Release of [3H]-NA evoked by 4 min exposure to 100 mM K+ could be partially inhibited by 5 microM nifedipine and partially inhibited by 100 nM omega-conotoxin GVIA (omega-CgTx). When nifedipine and omega-CgTx were added together, evoked release was inhibited by approximately 93%. 3. K(+)-evoked [3H]-NA release was inhibited by > 90% by pretreatment of cells for 2 min with muscarine, carbachol or oxotremorine methiodide (each at 300 microM). For muscarine, inhibition of evoked release was both time- and concentration-dependent and was reversible. Muscarine also inhibited [3H]-NA release evoked by veratridine (28 microM) and replacement of extracellular Ca2+ with Ba2+, but not that evoked by the Ca2+ ionophore, A23187 (19 microM). 4. Residual K(+)-evoked [3H]-NA release measured in the presence of either nifedipine (5 microM) or omega-CgTx (100 nM) was inhibited by muscarine with a similar potency as release evoked in the absence of either Ca2+ channel blocker. Pretreatment of cells for 16-24 h with pertussis toxin (200 ng ml-1) did not affect K(+)-evoked release per se or the ability of muscarine to inhibit such release. 5. Muscarinic inhibition of K(+)-evoked [3H]-NA release was potently antagonized by pirenzepine (pA2 8.14) and by hexahydrosiladiphenidol (pA2 9.03), suggesting the involvement of an M1 receptor. 6. Our results demonstrate that 100 mM K+-evoked release of [3H]-NA from the human neuroblastoma is mediated by activation of both L- and N-type Ca2+ channels. Activation of muscarinic Ml receptors can inhibit release via a pertussis toxin-insensitive mechanism which involves non-selective inhibition of L- and N-type Ca2+ channels.
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PMID:Muscarinic (M1) receptor-mediated inhibition of K(+)-evoked [3H]-noradrenaline release from human neuroblastoma (SH-SY5Y) cells via inhibition of L- and N-type Ca2+ channels. 783 16

The human neuroblastoma cell line SH-SY5Y, maintained at confluence for 14 days, released [3H]-noradrenaline ([3H]NA) when stimulated with either the muscarinic receptor agonist methacholine or bradykinin. The major fraction of release was rapid, occurring in < 10 s, whereas nicotine-evoked release was slower. When the extracellular [Ca2+]e) was buffered to approximately 50-100 nM, release evoked by nicotine was abolished, whereas that in response to methacholine or bradykinin was reduced by approximately 50% with EC50 values of -5.46 +/- 0.05 M and -7.46 +/- 0.06 M (log 10), respectively. Methacholine and bradykinin also produced rapid elevations of both inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and intracellular free [Ca2+] ([Ca2+]i). These elevations were reduced at low [Ca2+]e and under these conditions the EC50 values for peak elevation of [Ca2+]i were -6.00 +/- 0.14 M for methacholine and -7.95 +/- 0.34 M for bradykinin (n = 3 for all EC50 determinations). At low [Ca2+]e, depletion of nonmitochondrial intracellular Ca2+ stores with the Ca(2+)-ATPase inhibitor thapsigargin produced a transient small elevation of [Ca2+]i and a minor release of [3H]NA. At low [Ca2+]e, thapsigargin abolished elevation of [Ca2+]i in response to methacholine and bradykinin and completely inhibited their stimulation of [3H]NA release. It is proposed, therefore, that Ca2+ release from Ins (1,4,5)P3-sensitive stores is a major trigger of methacholine- and bradykinin-evoked [3H]NA release in SH-SY5Y cells.
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PMID:Mobilization of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores supports bradykinin- and muscarinic-evoked release of [3H] noradrenaline from SH-SY5Y cells. 786 Nov 49


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