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)

IgGs from two LEMS patients applied to human neuroblastoma IMR32 cells reduced the density of low- (LVA; T) and high-threshold (HVA; L and N) Ba2+ currents by different percentages: 36% (LVA) and 56% (HVA) for one and 48% and 45% for the other. A pharmacological assay of IgGs action based on the block of L-type channel by nifedipine and on the delayed activation of N-type channel by noradrenaline, indicated a preferential inhibition of the N-type current in IMR32 cells (55% and 47% for the two patients). The L-type current, contributing to approximately one-third of the total, was also depressed by LEMS IgGs but to a minor degree (49% and 30%). Except for an increase of single N-type channel inactivation, LEMS antibodies preserved the elementary properties of single HVA channels, suggesting that the macroscopic current reduction after IgGs treatment is likely due to a decrease in the number of active HVA Ca2+ channels.
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PMID:Inhibition of low- and high-threshold Ca2+ channels of human neuroblastoma IMR32 cells by Lambert-Eaton myasthenic syndrome (LEMS) IgGs. 789 70

In order to assess the neuronal-like properties of a human neuroblastoma cell line obtained by stable transfection of the estrogen receptor (SK-ER3) a series of quantitative measurements of the activity of two neurotransmitter-related enzymes: tyrosine hydroxylase (TH) and monamine oxidase (MAO), and of catecholamine concentrations were performed. When compared to the parental SK-N-BE cell line, the stably transfected SK-ER3 cells show a more pronounced dopaminergic phenotype. The immunoreactivity to a TH antibody is in fact increased and the ratio between dopamine and noradrenaline concentrations is elevated. Treatment with estradiol further enhances the expression of this phenotype. Interestingly, in the transfected cell line MAO-A activity is decreased and further reduced by estrogen treatment. This finding substantiated by previous reports indicates that our model system might represent an interesting tool for the study of the pharmacological treatments of estrogen-induced pathological responses of nervous cells.
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PMID:Estrogen modulation of catecholamine synthesis and monoamine oxidase A activity in the human neuroblastoma cell line SK-ER3. 790 62

The effect of hypoglycaemic, hypoxic, and ischaemic conditions on high-affinity neurotransmitter transport was studied in the human astrocytoma clone D384 and the human neuroblastoma clone SH-SY5Y. Both cell lines expressed a sodium-dependent glutamate/aspartate transporter. Km values for D-[3H]aspartate uptake were 6.1 +/- 0.9 microM for D384 cells and 5.3 +/- 0.3 microM for SH-SY5Y cells (mean +/- SEM of three experiments). In addition, SH-SY5Y, but not D384, expressed a sodium-dependent noradrenaline transporter with Km = 0.6 +/- 0.1 microM (mean +/- SEM of three experiments). Up to 3 h of hypoglycaemic conditions had no effect on neurotransmitter uptake or on ATP levels of each cell line. In sharp contrast, during hypoxic conditions, the uptake of D-[3H]-aspartate and [3H]noradrenaline declined by 43-56% within 5 min. These reduced rates of neurotransmitter uptake were maintained over 30 min of hypoxic conditions. Five minutes of ischaemic conditions caused similar reductions in neurotransmitter uptake rates. A correlation between reductions in rates of neurotransmitter uptake and in ATP levels was observed for each cell line. Results are discussed in relation to other brain preparations, which are used as models of the nervous system to study the effects of ischaemic conditions on neurotransmitter and energy metabolism.
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PMID:Effects of ischaemic conditions on uptake of glutamate, aspartate, and noradrenaline by cell lines derived from the human nervous system. 791 90

1. The roles of both Ca2+ and adenosine 3':5'-cyclic monophosphate (cyclic AMP) in carbachol and K(+)-stimulated [3H]-noradrenaline release from SH-SY5Y human neuroblastoma cells were examined. 2. Both carbachol and K+ caused a time- and dose-related stimulation of [3H]-noradrenaline release. The release event in perfused cells was monophasic. Half-maximum stimulation measured in statically incubated (3 min) cells was 38 +/- 4 microM and 63 +/- 4 mM respectively. K+ (100 mM, added)-evoked release was greater than that produced by carbachol (1 mM). 3. Both carbachol and K+ caused a time- and dose (measured at 3 min)-related stimulation of cyclic AMP formation with half-maximum stimulation occurring at 5 +/- 1 microM and 49 +/- 2 mM respectively. In contrast to its effects on release, carbachol produced a greater stimulation of cyclic AMP formation than K+. 4. K(+)-stimulated [3H]-noradrenaline release was entirely dependent on Ca2+ entry as 2.5 mM Ni2+ abolished release. However, carbachol-evoked (1 mM) release appeared to be unaffected by Ni2+ pretreatment. 5. These data suggest that in SH-SY5Y cells, elevated cyclic AMP levels are not directly involved in [3H]-noradrenaline release. In addition, carbachol-stimulated release is largely independent of extracellular Ca2+ possibly implying a role for intracellular stored Ca2+ in the release process.
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PMID:Studies on the mechanism of [3H]-noradrenaline release from SH-SY5Y cells: the role of Ca2+ and cyclic AMP. 801 57

1. This study examined the regulation of calcium currents in differentiated NG108-15 cells that had been stably transfected with cDNA encoding the short isoform of the human D2 dopamine receptor. Whole cell calcium currents were recorded by nystatin-perforated patch clamp recording. 2. Transient low-threshold calcium currents elicited by depolarizations from -100 mV to -20 mV were reversibly depressed by NiCl2 (84 +/- 8% at 30 microM; n = 3) and by omega-agatoxin IVA (15 +/- 5%; 100 nM, n = 7). These currents were unaffected by hD2 receptor activation. 3. High-threshold calcium currents elicited by depolarizations from -80 mV to 0 mV were partly blocked by omega-conotoxin GVIA (67 +/- 6% at 100 nM, n = 4) and by the subsequent addition of the dihydropyridine, nisoldipine (94 +/- 3% at 1 microM). Consistent with the presence of at least two distinct types of high-threshold calcium channels, nisoldipine alone (38 +/- 15% at 1 microM, n = 6) did not preclude the inhibition caused by omega-conotoxin GVIA (69 +/- 13% at 100 nM, n = 4). The residual current was completely blocked by 100 microM CdCl2 (98.8 +/- 0.4%, n = 7). 4. In hD2-transfected cells, but not untransfected cells, high-threshold currents were depressed by quinpirole (30 +/- 4% at 100 nM; n = 15) with a pEC50 of 8.61 +/- 0.22 (n = 5), as well as by (-)-noradrenaline (28 +/- 5% at 1 microM, n = 9). Responses to both agonists were selectively antagonized by S-(-)sulpiride (100 nM) but not by the alpha-adrenoceptor antagonist, phentolamine (1O microM). The depression caused by (-)-noradrenaline was positively correlated with that of quinpirole for each cell(r2 = 0.91, slope = 0.99).5. hD2-receptor-mediated inhibition of high-threshold calcium currents was abolished by pretreatment of cells with omega-conotoxin GVIA (100 nM; n = 4). However, a component of the high-threshold current was reversibly depressed by omega-conotoxin GVIA (67% to 45% depression after 10 min wash). This current was also depressed by hD2 receptor activation (59 +/- 9% depression in 100 nM quinpirole, n = 3),and was completely blocked by nisoldipine (95 +/- 2% at 1 MicroM).6. These data demonstrate that activation of hD2(short) dopamine receptors can regulate both wconotoxinGVIA, and dihydropyridine-sensitive high-threshold calcium currents in neuroblastoma cells.Morever, the ability of human D2 dopamine receptors to regulate more than one type of calcium current supports the notion that these receptors have a diverse functional role in the central nervous system.
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PMID:Depression of high-threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108-15 cells. 803 91

Bradykinin (BK) evoked [3H]noradrenaline ([3H]NA) release from the human neuroblastoma SH-SY5Y and this was enhanced by pre-treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 8 min. This effect of BK was inhibited by 500 microM [D-Phe7]BK and 100 microM [Thi5,8,D-Phe7]BK but not by 500 microM [Des-Arg9,Leu8]BK. The BK (B1)-agonist [Des-Arg9]BK did not evoke [3H]NA release. This suggested that SH-SY5Y expressed BK (B2)-receptors coupled to the release of [3H]NA. BK acting at B2-receptors, also elevated intracellular calcium and depolarized SH-SY5Y cells. Although pre-treatment of SH-SY5Y cells with TPA enhanced BK-evoked [3H]NA release, the elevation of intracellular calcium [Ca2+]; was decreased by about 50%. BK-evoked release of [3H]NA in cells not pre-treated with phorbol ester was only 23% dependent on extracellular calcium. In comparison, following phorbol ester treatment approximately 40% of [3H]NA release was dependent on extracellular calcium. Nifedipine (5 microM), CoCl2 (1 mM) and NiCl2 (1 mM) inhibited NA release in SH-SY5Y cells pre-treated with TPA by 16.0, 47 and 44%, respectively. The results of this study showed that BK, acting at B2-receptors, activated [3H]NA release in SH-SY5Y. Part of this effect appeared to be due to activation of L-type calcium channels but the majority of BK-evoked [3H]NA release in SH-SY5Y cells appeared to depend on [Ca2+]i.
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PMID:Bradykinin-evoked release of [3H]noradrenaline from the human neuroblastoma SH-SY5Y. 804 27

We have examined the effect of fentanyl on [3H]noradrenaline release in a human neuroblastoma cell preparation, SH-SY5Y. Fentanyl produced a significant, concentration-dependent inhibition of [3H]noradrenaline release with IC50 values of 5.5 x 10(-6) mol litre-1 and 15.5 x 10(-6) mol litre-1 for carbachol- and potassium-evoked release, respectively. The small difference in IC50 between the two evoking stimuli may be explained by the weak binding affinity of fentanyl to muscarinic receptors (Ki = 570 nmol litre-1). The minimum concentrations at which a significant effect was observed were 0.3 x 0.10(-6) mol litre-1 and 10.0 x 10(-6) mol litre-1 for carbachol- and potassium-evoked release, respectively; these values are considerably in excess of the serum concentration of fentanyl required to produce analgesia. Naloxone failed to antagonize the fentanyl inhibition and, furthermore, morphine and an enkephalin had no effect on evoked release, implying a non-opioid receptor mediated effect.
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PMID:Fentanyl inhibits the release of [3H]noradrenaline from SH-SY5Y human neuroblastoma cells. 811 May 61

This study reports experience in the estimation of urinary catecholamines (uCATs) and their metabolites in the diagnosis and follow-up of neuroblastoma. Random urine samples were assayed for dopamine, noradrenaline and adrenaline, together with their metabolites 4-hydroxy 3-methoxymandelic acid (HMMA) and homovanillic acid (HVA), using HPLC with electrochemical detection. Twenty of 21 patients had elevation of one or more uCATs metabolites at diagnosis. Patients were monitored serially from diagnosis and, in those patients who had delayed resection of primary tumour (n = 13), particular attention was paid to levels at the pre-surgical evaluation as an indicator of persistence of viable disease at the time of surgery; dopamine proved to be the most accurate indicator of persistent disease at this time. Five of these patients developed recurrent disease, 4 of whom had elevation of two or more uCATs metabolites at the time of relapse. Several conclusions can be drawn from this study: (a) results for HMMA, HVA and dopamine in random urine samples will detect all but the most biochemically immature or inert tumours; (b) dopamine may be the most reliable indicator of persistent disease and (c) noradrenaline and adrenaline measurements were of little benefit. As results are expressed in relation to urinary creatinine, excretion of which may be affected by dietary protein and is therefore not constant, borderline results should be repeated.
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PMID:Interpretation of random urinary catecholamines and their metabolites in neuroblastoma. 819 81

Meta-[211At]astatobenzylguanidine ([211At]MABG) is an astatinated analogue of meta-iodobenzylguanidine (MIBG) that could be of value for therapeutic applications. The initial goal of this study was to determine whether [211At]MABG is taken up, like MIBG, by a specific uptake-I mechanism. Norepinephrine and desipramine (DMI) decreased [211At]MABG uptake in SK-N-SH human neuroblastoma cells. This uptake was found to be energy-dependent: In mice, pre-treatment with DMI reduced uptake of [211At]MABG at 1 hr post-injection in the adrenal and in the heart. Tetrabenazine at a dose of 40 mg/kg reduced uptake of [211At]MABG in the mouse heart in vivo (69% of control) whereas up to 100 microM of tetrabenazine did not affect the in vitro uptake of [211At]MABG in SK-N-SH cells. In SK-N-SH cells, 53% and 38%, respectively, of the initial uptake of [211At]MABG was retained at 4 hr and 6 hr. For no-carrier-added (n.c.a.) [131I]MIBG these values were similar, 60% and 48%. The ability of SK-N-SH cells to incorporate [3H]thymidine was reduced to less than 50% of control values when treated with as little as 3.2 nCi of [211At]MABG. In contrast, no significant reduction in the thymidine uptake was observed, even with 80 nCi of n.c.a. MIBG.
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PMID:Meta-[211At]astatobenzylguanidine: further evaluation of a potential therapeutic agent. 820 83

Opiate receptor occupation leads to a variety of intracellular events including inhibition of adenylyl cyclase and cAMP formation. We have examined the opiate binding characteristics, effects on cAMP formation and [3H]noradrenaline release of morphine, morphine-6 (M6G) and -3 (M3G)-glucuronides, and fentanyl in SH-SY5Y human neuroblastoma cells. M6G and M3G are the major metabolites of morphine formed in vivo whose cellular action remains to be fully elucidated. In binding experiments morphine (affinity, K50 = 96 nM) and fentanyl (K50 = 99 nM) were more potent than M6G (K50 = 393 nM), while M3G was inactive. However, for cAMP inhibition morphine (half maximum inhibition, IC50 = 193 nM) and M6G (IC50 = 113 nM) were roughly equipotent, with fentanyl (IC50 = 27 nM) being more potent and producing a greater maximum inhibition (56%). M3G was inactive. These in vitro data are in general agreement with the in vivo effects of these glucuronides. Moreover, all of the opiates tested failed to inhibit K(+)-evoked release of [3H]noradrenaline. Whilst these data do not support a role for cAMP in neurotransmitter release, alterations in cAMP formation may still have a role to play in the mechanism of analgesia.
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PMID:Effects of morphine and its metabolites on opiate receptor binding, cAMP formation and [3H]noradrenaline release from SH-SY5Y cells. 821 64


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