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)

As previously reported by this laboratory, an endogenous factor capable of inhibiting the specific binding of the radiolabeled cannabinoid agonist [3H]CP-55940 to its receptor can be released from nerve terminals in response to an influx of Ca++ induced by an ionophore (Evans et al., 1992). In the present report, we provide evidence that the endogenous ligand for the cannabinoid receptor can be released in response to a depolarizing stimulus (75 mM K+) in the presence of extracellular Ca++. K(+)-evoked release was not observed in the absence of extra-cellular Ca++ and was reduced by the specific calcium channel blockers verapamil and omega-conotoxin. The efflux of cannabinoid receptor binding activity is greatest within 2 min of stimulation with the Ca++ ionophore A23187. Within this period of time, the cannabinoid receptor binding activity was enhanced by the presence of a cocktail of peptidase inhibitors. Examination of the contribution of individual inhibitors for enhancing high K(+)-released material revealed a selectivity for captopril and thiorphan. The specificity of the released factor for the cannabinoid receptor was corroborated by its ability to compete with the aminoalkylindole radioligand [3H]WIN-55212 for binding to this receptor. Fractions from a semi-purified sample of the effluent demonstrated binding to the cannabinoid receptor and behaved as agonists in that these fractions could inhibit adenylate cyclase activity in neuroblastoma membrane preparations.
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PMID:Endogenous cannabinoid receptor binding activity released from rat brain slices by depolarization. 813 40

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

A neuroblastoma cell line of human origin was used as an in vitro model system to examine early effects on inhibition of neuropathy target esterase (NTE, also known as neurotoxic esterase) in the presence of agents belonging to classes of chemicals previously demonstrated to modify organophosphorus-induced delayed neuropathy in hens. For this study, differentiated SY-5Y cells were treated for up to 10 min with mipafox, an organophosphorus compound, and NTE inhibition was determined when cells exposed to mipafox were also exposed to the carbamate, aldicarb, and to the calcium channel blocker, verapamil. Cells were exposed to aldicarb or verapamil 5 min before, at the same time, or 2 min after mipafox. Less NTE inhibition was observed when either aldicarb or verapamil was included in the incubation of SY-5Y cells with mipafox. Effects of aldicarb and verapamil on NTE inhibition in differentiated SY-5Y cells were similar to effects in chicken brain homogenates. These results indicate that NTE inhibition can be detected in neuroblastoma cells, that these cells respond in a manner similar to chicken brain, and that mipafox-induced inhibition of NTE can be decreased in the presence of aldicarb or verapamil.
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PMID:Modification of mipafox-induced inhibition of neuropathy target esterase in neuroblastoma cells of human origin. 833 99

Chlordiazepoxide is a benzodiazepine that is widely used as a minor tranquilizer. It is also effective in the treatment of acute alcohol withdrawal. In this setting, chlordiazepoxide acts as a sedative and prevents the development of epileptiform activity. Although benzodiazepines are known to augment gamma-aminobutyric acid-activated chloride channels, an action which at least partially accounts for their anticonvulsant properties, there is some evidence to suggest that voltage-activated calcium channels may also be the target of these agents. We therefore studied the effect of chlordiazepoxide in blocking two distinct types of voltage-activated calcium channels in N1E-115 neuroblastoma cells. Chlordiazepoxide reversibly blocked calcium channels in both closed and open configurations. It was slightly more potent in blocking the transient (T-type or type I) than the long-lasting (L-type or type II) type of calcium channels with apparent Ki values of 311 and 398 microM, respectively. In the presence of chlordiazepoxide, the currents of both types of calcium channel currents decayed more quickly than control, an observation that suggests open channel block. Chlordiazepoxide-induced block of T-type calcium channels was use dependent, increasing with an increase in stimulus frequency. This was due primarily to the acceleration of current decay and slowing of recovery from inactivation by chlordiazepoxide. These calcium channel blocking actions could contribute some to the sedative and anticonvulsant properties of chlordiazepoxide in patients suffering from acute alcohol withdrawal and in electric shock-induced seizures in animal models.
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PMID:Chlordiazepoxide block of two types of calcium channels in neuroblastoma cells. 838 Aug 61

Extracellular ATP has neurotransmitter-like properties in the CNS and PNS that are mediated by a cell-surface P2 purinergic receptor. In the present study, we have extensively characterized the signal transduction pathways that are associated with activation of a P2U receptor in a cultured neuroblastoma x glioma hybrid cell line (NG108-15 cells). The addition of > or = 1 microM ATP to NG108-15 cells caused a transient increase in [Ca2+]i that was inhibited by 40% when extracellular calcium was chelated by EGTA. ATP concentrations > or = 500 microM also elicited a sustained increase in [Ca2+]i that was inhibited when extracellular calcium was chelated by EGTA. The increase in [Ca2+]i elicited by ATP occurred concomitantly with the hydrolysis of [32P]-phosphatidylinositol 4,5-bisphosphates and an increase in the level of inositol 1,4,5-trisphosphate. ATP also caused a time- and dose-dependent increase in levels of [3H]inositol monophosphates in lithium-treated cells. Separation of the inositol monophosphate isomers by ion chromatography revealed a specific increase in the level of inositol 4-monophosphate. The magnitude of the increase in [Ca2+]i elicited by ATP correlated with the concentration of the fully ionized form of ATP (ATP4-) in the medium and not with the concentration of magnesium-ATP (MgATP2-). Similar to ATP, UTP also induced polyphosphoinositide breakdown, inositol phosphate formation, and an increase in [Ca2+]i. ADP, ITP, TTP, GTP, ATP gamma S, 2-methylthio ATP, beta, gamma-imidoATP or 3'-O-(4-benzoyl)benzoylATP, but not CTP, AMP, beta, gamma-methylene ATP, or adenosine, also caused an increase in [Ca2+]i. In cells labeled with [32P]P(i) or [14C]-arachidonic acid, ATP caused a transient increase in levels of labeled phosphatidic acids, but had no effect on levels of arachidonic acid. The increase in phosphatidic acid levels elicited by ATP apparently was not due to activation of a phospholipase D because ATP did not induce the formation of phosphatidylethanol in [14C]myristic acid-labeled cells incubated in the presence of ethanol. These findings support the hypothesis that a P2 nucleotide receptor in NG108-15 cells is coupled to a signal transduction pathway involving the activation of a phospholipase C and a plasma membrane calcium channel, but not the activation of phospholipases A2 and D.
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PMID:Signal transduction pathways coupled to a P2U receptor in neuroblastoma x glioma (NG108-15) cells. 838 62

1. Putrescine has been implicated in modulating cytoplasmic calcium concentration and is correlated with selective neuronal vulnerability in cerebral ischaemia. In order to determine whether putrescine modulates voltage-activated calcium channels, whole-cell and single channel patch clamp experiments were performed with N1E-115 mouse neuroblastoma cells. 2. L-type calcium channel currents showed a 34 +/- 21% increase (n = 6 cells) during external application of 1 mM putrescine. There was no change in the kinetics of the current and no shift in the current-voltage relationship along the voltage axis. 3. T-type calcium channel currents were not affected by 1 mM putrescine. 4. The effect of putrescine on single L-type calcium channels was studied using the cell-attached configuration of the patch clamp technique. Putrescine (5 mM) applied to the bathing solution, but not present in the pipette, caused an increase in open time of the single channel current without changing the conductance of the channel. In 345 depolarizing steps compiled from three cells, the number of channel openings longer than 3 ms increased from six to seventy-six, and the number of channel openings longer than 9 ms increased from zero to twenty-seven. This single channel study supports the hypothesis that putrescine acts on the L-type channel from the inside of the cell. 5. External application of 1 mM spermine and 1 mM spermidine had no effect on T- and L-type calcium channels. Thus, the effect of putrescine is probably not mediated by the higher polyamines. 6. In order to test whether the effect of putrescine is mediated by a second messenger, specific protein kinase C and cyclic AMP-dependent protein kinase inhibitors, staurosporine and KT5720, respectively, were applied prior to putrescine. When cells were preconditioned with 200 nM staurosporine, the increase of the L-type calcium current by 1 mM putrescine was inhibited. By contrast, 200 nM KT5720 did not inhibit the putrescine effect. Therefore, the increase of L-type channel currents by putrescine may be mediated by protein kinase C but not the cyclic AMP-dependent protein kinase. 7. The putrescine-induced enhancement of the L-type calcium channel activity may play an important role in calcium-induced neurotoxicity.
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PMID:The effect of polyamines on voltage-activated calcium channels in mouse neuroblastoma cells. 839 76

Calcium channel antagonists are drugs currently used in the treatment of neurological and cardiovascular disorders and occasionally produce parkinsonism and movement disorders as a side effect. We investigated the effects of calcium channel antagonists on the pharmacology of dopamine systems in vivo and in vitro. Flunarizine, cinnarizine, and diltiazem reduce the viability of dopamine-rich human neuroblastoma cells in vitro. These compounds plus verapamil, nifedipine, and nicardipine reduce 3H-spiperone binding to bovine striatal membranes, 3H-dopamine uptake, K(+)-induced 3H-dopamine release, and apomorphine-induced rotation, but not amphetamine-induced rotation, in 6-OH-dopamine-lesioned rats. Therefore, all calcium channel antagonists tested reduce dopamine neurotransmission in vitro and in vivo, whereas the evidence of toxicity for dopamine cells in vitro is restricted to flunarizine, cinnarizine, and diltiazem. The clinical relevance of these toxic effects may depend on several factors, including age, penetration across the blood-brain barrier, and types of calcium channels present in the different neuronal subtypes. On the other hand, the finding of dopamine-regulating properties not associated to neurotoxic effects in the dihydropyridines and verapamil provides new putative therapeutics tools for the treatment of neurologic disorders associated with dopamine hyperactivity.
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PMID:Effects of calcium antagonists on the dopamine system. 866 55

The expression of alpha 1-chimaerin, which encodes a neuron-specific GTPase-activating protein for p21rac, is spatially and temporally regulated in vivo. In vitro, expression of the mRNA of both alpha 1-chimaerin and its alternative spliced form, alpha 2-chimaerin, was up-regulated when human neuroblastoma SK-N-SH cells underwent neuronal-type differentiation in a serum-free medium. KCl-induced membrane depolarisation also specifically up-regulated alpha 1-chimaerin mRNA expression in SK-N-SH cells at the transcriptional level. The up-regulation of alpha 1-chimaerin expression by membrane depolarisation is not an immediate early event, and occurs 3 h after KCl treatment. It does not require de novo protein synthesis. The increase in calcium influx via the L-type voltage-sensitive calcium channel as the result of depolarisation is a key event leading to the up-regulation of alpha 1-chimaerin mRNA. alpha 1-Chimaerin expression was also found to respond positively to the hypertonic osmolarity changes. These results suggest that in vivo expression of alpha 1-chimaerin, a potential signal transduction molecule, may be regulated by neuronal/synaptic activity.
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PMID:Selective up-regulation of alpha 1-chimaerin mRNA in SK-N-SH neuroblastoma cells by K+/-induced depolarisation. 866

1. The effects of a range of metal ions were systematically studied at the mouse neuromuscular junction in order to investigate the type of calcium channel present at the nerve terminal. 2. Endplate potentials and miniature endplate potentials were recorded from the phrenic nerve diaphragm muscle preparation with glass microelectrodes. 3. Endplate potential amplitudes and quantal contents were reduced by manganese (IC50 220 microM), cadmium (IC50 11 microM), cobalt (IC50 350 microM), and nickel (IC50 420 microM). Miniature endplate potentials were not affected by these ions at concentrations equal to the IC50s. Gadolinium did not reduce endplate potentials up to 100 microM. 4. Comparisons made with known channel types in neuroblastoma cell lines suggest that the calcium channels at the motor nerve terminal are different from those types studied in the cell lines, although most similarity is shown to the high-voltage activated calcium channel types.
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PMID:Relative potencies of metal ions on transmitter release at mouse motor nerve terminals. 873 72

The human neuroblastoma cell line SH-SY5Y expresses the 'orphan' opioid receptor (ORL1). We have demonstrated that nociceptin, the putative endogenous ligand for ORL1, produces a concentration-dependent inhibition of the N-type calcium channel current in these cells (IC50 42 nM). In addition, in the presence of carbachol, nociceptin increased the intracellular concentration of Ca2+ (EC50 60 nM). Both effects of nociceptin were blocked by pertussis toxin pretreatment but not by the opioid antagonists CTAP (1 microM), naltrindole (1 microM) and naloxone (10 microM).
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PMID:The effect of nociceptin on Ca2+ channel current and intracellular Ca2+ in the SH-SY5Y human neuroblastoma cell line. 873 15


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