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)

Veratridine or high potassium concentration increased guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuroblastoma cells of clone N1E-115 without affecting levels of adenosine 3',5'-cyclic monophosphate (cAMP). The increases in cGMP appear to be a direct result of the depolarizing action of these agents and not due to the action of substances released from the cells upon depolarization. The increase in cGMP produced by depolarization was dependent upon extracellular calcium and could be prevented by the calcium channel blockers D600 and cobalt. Carbachol, acting on muscarinic acetylcholine receptors, also caused a calcium-dependent increase in cGMP in these cells. The carbachol and potassium effects were additive from 5 to 100 mM potassium and from 1 to 3 mM calcium. The carbachol response was nearly as sensitive as the potassium response to inhibition by D600 but was much less sensitive to inhibition by cobalt. The results suggest that depolarization increases cGMP levels in these cells by opening voltage-sensitive calcium channels and that activation of muscarinic receptors opens separate, voltage-insensitive calcium channels.
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PMID:Voltage-sensitive calcium channels regulate guanosine 3',5'-cyclic monophosphate levels in neuroblastoma cells. 21 20

mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity.
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PMID:Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells. 127 57

The psychoactive properties of Cannabis sativa and its major biologically active constituent, delta 9-tetrahydrocannabinol, have been known for years. The recent identification and cloning of a specific cannabinoid receptor suggest that cannabinoids mimic endogenous compounds affecting neural signals for mood, memory, movement, and pain. Using whole-cell voltage clamp and the cannabinomimetic aminoalkylindole WIN 55,212-2, we have found that cannabinoid receptor activation reduces the amplitude of voltage-gated calcium currents in the neuroblastoma-glioma cell line NG108-15. The inhibition is potent, being half-maximal at less than 10 nM, and reversible. The inactive enantiomer, WIN 55,212-3, does not reduce calcium currents even at 1 microM. Of the several types of calcium currents in NG108-15 cells, cannabinoids predominantly inhibit an omega-conotoxin-sensitive, high-voltage-activated calcium current. Inhibition was blocked by incubation with pertussis toxin but was not altered by prior treatment with hydrolysis-resistant cAMP analogues together with a phosphodiesterase inhibitor, suggesting that the transduction pathway between the cannabinoid receptor and calcium channel involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. However, the development of inhibition is considerably slower than a pharmacologically similar pathway used by an alpha 2-adrenergic receptor in these cells. Our results suggest that inhibition of N-type calcium channels, which could decrease excitability and neurotransmitter release, may underlie some of the psychoactive effects of cannabinoids.
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PMID:Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. 131 42

The effect of nifedipine dissolved in different solvents on the two types of calcium channel currents in neuroblastoma cells was investigated using the whole cell version of the patch clamp technique. Nifedipine dissolved in dimethylsulfoxide (nifedipine/DMSO) decreased the transient calcium channel (T channel) current by 50% at a concentration of 10 microM. This inhibitory effect was concentration-dependent and reversible. In contrast, T channel currents were not inhibited by nifedipine at a similar concentration dissolved in acetone or ethanol. Further experiments were carried out with dried nifedipine/DMSO. Dried nifedipine/DMSO powder re-dissolved in acetone or ethanol at a concentration of 10 microM decreased the T channel current by 32% and 37%, respectively. In addition, within the concentration range of 10 nM to 100 microM nifedipine/DMSO inhibited the long-lasting calcium channel (L channel) current more effectively than did nifedipine dissolved in acetone. The concentration of solvent (DMSO, ethanol, acetone) in the bath was fixed at 0.3% to reach different final concentrations of nifedipine. Solvents alone at a final concentration of 0.3% did not show any effect on T or L channel currents. UV absorbance measurements indicated that the combination of nifedipine, solvent and bath solution did not result in precipitation of the dihydropyridine during the experimental protocol. It is concluded that when DMSO is used as the solvent, nifedipine is not only a more effective L channel antagonist but also a T channel antagonist in neuroblastoma cells.
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PMID:Modification by solvents of the action of nifedipine on calcium channel currents in neuroblastoma cells. 132 Feb 11

N-type calcium channels are omega-conotoxin (omega-CgTx)-sensitive, voltage-dependent ion channels involved in the control of neurotransmitter release from neurons. Multiple subtypes of voltage-dependent calcium channel complexes exist, and it is the alpha 1 subunit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel alpha 1B subunits were deduced by the characterization of overlapping complementary DNAs. Two forms (alpha 1B-1 and alpha 1B-2) were identified in human neuroblastoma (IMR32) cells and in the central nervous system, but not in skeletal muscle or aorta tissues. The alpha 1B-1 subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal beta 2 and alpha 2b subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by omega-CgTx but was insensitive to dihydropyridines. The alpha 1B-1 alpha 2b beta 2-transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) omega-CgTx binding sites. Co-expression of the beta 2 subunit was necessary for N-type channel activity, whereas the alpha 2b subunit appeared to modulate the expression of the channel. The heterogeneity of alpha 1B subunits, along with the heterogeneity of alpha 2 and beta subunits, is consistent with multiple, biophysically distinct N-type calcium channels.
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PMID:Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. 132 1

P-glycoprotein, the product of the multidrug resistance (MDR1) gene, is an ATP-driven transmembrane pump that increases the resistance of cells by actively exporting toxic chemicals. In addition to transporting anticancer drugs, P-glycoprotein has been reported to extrude a variety of lipophilic drugs, such as calcium channel blockers, phenothiazines, cyclosporines etc. Interestingly, recent experiments suggest that steroid hormones may be physiologic substrates for P-glycoprotein. In addition, there exists a family of transporter genes with high structural homology to P-glycoprotein, the so-called ABC (ATP-binding casette) family. Although the physiological ligands for most of these transporters are unknown, there is increasing evidence that peptides may be transported by some of these proteins. Thus, the a-factor, a farnesylated pheromone with 13 amino acids, is exported from yeast cells by the product of the STE6 gene, a transporter protein with high homology to P-glycoprotein. Recently, we have cloned a novel member of the ABC-transporter gene family from neuroblastoma x glioma hybrid (NG-108-15) cells. This putative transporter gene ("NG-TRA") is expressed in the adrenal gland, kidney and in the brain. High amounts of NG-TRA mRNA are found in a variety of human brain tumors. Whether NG-TRA and/or other MDR-related transporters are involved in the transport of steroids, peptide hormones or growth factors remains to be established. If so, the cellular export of hormones by active pumps may represent a new mechanism of hormone secretion.
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PMID:New mechanisms of hormone secretion: MDR-like gene products as extrusion pumps for hormones? 135

This report describes the effect of Bay K-8644 dissolved in various solvents on two types of calcium channel currents in neuroblastoma cells. Transient calcium channel (T channel) currents were not affected by Bay K-8644 dissolved in ethanol (EtOH) or polyethylene glycol (PEG). However, at the same concentration of 0.6 microM, Bay K-8644 dissolved in dimethylsulfoxide (DMSO) (Bay K-8644/DMSO) decreased the T channel current by 50%. The concentration of all three solvents in the bath was fixed at 0.3% to reach different final concentrations of Bay K-8644. At this fixed solvent concentration, the inhibitory effect of Bay K-8644/DMSO on T channel currents was dose-dependent; the solvents alone did not have any effect on T channel currents; and DMSO pretreatment of cells did not render the T channel current sensitive to Bay K-8644 dissolved in EtOH or PEG. Bay K-8644/DMSO was dried using a flash evaporator and redissolved in EtOH or PEG. Dried Bay K-8644 that was redissolved in EtOH or PEG to achieve a final concentration of 0.6 microM inhibited T channel currents by 39 or 35%, respectively. Furthermore, Bay K-8644 (10 nM) increased L channel currents by 80% with DMSO, but only 30% with EtOH as the solvent. These results show that in neuroblastoma cells Bay K-8644/DMSO, within the concentration range examined, is a T channel antagonist and more effective L channel agonist than Bay K-8644 dissolved in the two other solvents.
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PMID:Bay K-8644 in different solvents acts as a transient calcium channel antagonist and a long-lasting calcium channel agonist. 137 52

Our study explores the mechanisms behind neurite galvanotropism. Using phase, differential interference contrast and ratiometric fluorescence microscopy, we reveal four responses of N1E-115 mouse neuroblastoma cells to 0.1-1.0 mV/microns uniform DC electric fields: cathode-directed neurite initiation and elongation, cathode-biased growth cone filopodial protrusions, transient cathode-localized calcium increases, and persistent cathode-localized membrane depolarizations. These newly demonstrated events are temporally and spatially correlated, suggesting that they are causally related. The calcium increases are prevented by calcium channel blockers and by the removal of extracellular calcium. We therefore propose that the observed field-induced membrane depolarizations activate voltage-dependent calcium channels, resulting in cathode-localized calcium influx. This, in turn, may initiate the observed cathode-biased growth cone filopodial protrusions, followed by the cathode-directed neurite elongation.
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PMID:Localized membrane depolarizations and localized calcium influx during electric field-guided neurite growth. 152 23

1. Single low-threshold inactivating (LTI or T-type) Ca2+ channels of undifferentiated neuroblastoma cells (clone N1E-115) were investigated using the patch-clamp technique. 2. Single-channel conductance, gi, for Ca2+, Sr2+ or Ba2+ as a permeant cation was similar (7.2 pS). Mean channel open time, tau op, was also practically independent of the divalent ion species; it decreased from 0.7 to 0.3 ms between -40 and 0 mV. 3. Modification of the calcium channel selectivity by lowering the external Ca2+ concentration to 10(-8) M produced an increase in gi for Na+ and Li+ ions and a shift of potential-dependent characteristics in the hyperpolarizing direction. Voltage sensitivity and absolute values of tau op were also changed. These changes were dependent on both permeant monovalent ion type and concentration. 4. At high [Na+]o, tau op was almost potential independent (congruent to 0.3 ms). Decrease in [Na+]o and substitution of Li+ for Na+ increased tau op and the steepness of its potential dependency. 5. The divalent and monovalent cations that were tested had much smaller effect on the mean intraburst shut time, tau cl(f), which was nearly independent of membrane potential (congruent to 0.6 ms). By contrast, mean burst duration was strongly potential dependent and noticeably affected by permeant ion type. 6. All kinetic changes were analysed in terms of a four-state sequential model for channel activation. According to this model the channel enters the open state through three closed states. Transitions between closed states can be formally related to the transmembrane movement of two charged gating particles (m2 process). The interaction between ion flux and a sterical region of the Ca2+ channel selectivity filter may, depending on ion transfer rate and ionic radius, lead to a local increase of the dielectric constant, resulting in redistribution of the electric field and changes in potential dependency of tau op.
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PMID:The effect of permeant ions on single calcium channel activation in mouse neuroblastoma cells: ion-channel interaction. 166 37

The predominant consequences of mu-opioid-receptor activation are depression of both neuronal activity and transmitter release. Mu-Opioid agonists have previously been observed to increase a potassium conductance and to inhibit adenylate cyclase. We now report that activation of mu-opioid receptors directly decreases the N-type calcium-channel current in a differentiated, human neuroblastoma cell line (SH-SY5Y). The coupling between the mu-opioid receptor and the calcium channel involves a pertussis toxin-sensitive G protein and is independent of changes in adenylate cyclase activity. The inhibition of the calcium-channel current is voltage dependent because it is largely overcome by strong membrane depolarization. It is not associated with changes in the kinetics of current inactivation. Therefore, the mu-receptor belongs to the superfamily of G-protein-coupled, inhibitory neurotransmitter receptors which modulate the activity of calcium and potassium channels and adenylate cyclase.
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PMID:Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current. 167 47


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