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)

The human neuroblastoma clone SH-SY5Y expresses potassium-, carbachol-, and calcium ionophore A23187-evoked, calcium-dependent release of [3H]noradrenaline. Release in response to carbachol and potassium was greater than additive. Atropine (Ki = 0.33 nM), hexahydrosiladifenidol (Ki = 18 nM), and pirenzepine (Ki = 1,183 nM) completely inhibited the carbachol-evoked noradrenaline release, an order of potency suggesting that an M3 receptor was linked to release. In contrast, noradrenaline release was only partially inhibited by the M2-selective antagonists methoctramine (10(-4) M) and AFDX-116 (10(-4) M), by approximately 14 and 46%, respectively. The nicotinic antagonist d-tubocurarine (10(-4) M) resulted in a partial inhibition of release, a finding suggesting that a nicotinic receptor may also be involved. SH-SY5Y provides a suitable cell line in which to study the biochemical mechanisms underlying the cholinergic receptor regulation of noradrenaline release.
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PMID:Potassium- and carbachol-evoked release of [3H]noradrenaline from human neuroblastoma cells, SH-SY5Y. 190 96

The steady-state effects and rate of action of 4-aminopyridine (4-AP) on normal and chloramine-T (CL-T)-modified voltage-dependent potassium (K) currents were studied in neuroblastoma cells with the whole-cell voltage-clamp current recording technique. 4-AP apparently slows both the activation and inactivation of the normal current but does not modify the time course of the CL-T-modified current. These differential effects of 4-AP are interpreted as resulting from the existence of two types of K channels with different 4-AP sensitivities under normal conditions and similar 4-AP sensitivities after CL-T, which furthermore slows their inactivation [8, 9]. While the onset of 4-AP action on the normal current is delayed and can be described by the difference of two exponentials, the onset of 4-AP action on CL-T-modified current starts immediately after the external application of the drug and can be described by the sum of two exponentials. The 4-AP-induced block of the normal current exhibits use-dependent features and is relieved by long conditioning depolarizations. In contrast, the block of the CL-T-modified current is not use-dependent. At high 4-AP concentrations (1-10 mM), the steady-state block of the normal current reaches a saturating value of 95%, while the steady-state block of the CL-T-modified current and the "unblocked" normal current only reaches a saturating value of 35%. The results suggest that CL-T inhibits a channel or membrane constituent which contributes to the inactivation of channels and increases their apparent affinity for 4-AP when they are in closed or open states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of 4-aminopyridine with normal and chloramine-T-modified K channels of neuroblastoma cells. 194 66

Bradykinin triggered intracellular Ca mobilizations and ionic conductance changes were studied in the neuroblastoma x glioma hybrid cell line NG108-15 using Ca-sensitive fluorescent indicator fura-2 under patch pipette whole cell voltage clamp condition. The time course of outward current induced by bradykinin was closely related to the time-course of [Ca2+]i change. Following application of bradykinin, [Ca2+]i increased transiently and then decreased below the basal level before bradykinin application. The inward currents activated by step-depolarization were suppressed after bradykinin application, but the time-course of the suppression did not go in parallel with the [Ca2+]i changes: the suppression started before the [Ca2+]i change emerged and outlasted the phase of [Ca2+]i increase. Both transient type and long-lasting type Ca current were suppressed by bradykinin. [Ca2+]i increase induced by high potassium depolarization was suppressed by bradykinin. Pertussis toxin did not affect the Ca transient nor the suppression of Ca channel induced by bradykinin. Our results suggest that the modifications of ionic channels by bradykinin could be through the other mechanisms than the well established activation of the G-protein leading to the IP3 mechanisms and that the bradykinin receptor might couple with the pertussis toxin-insensitive G protein which regulates the calcium channels.
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PMID:Mobilization of intracellular Ca2+ and suppression of inward currents in a neuronal hybrid cell line triggered by bradykinin. 196 37

Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.
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PMID:Free radicals mediate actions of oxyhemoglobin on cerebrovascular smooth muscle cells. 199 46

1. The patch-clamp method was applied to the study of ionic currents activated by depolarization of undifferentiated IMR-32 human neuroblastoma cells. Whole-cell sodium and potassium currents and single potassium ion channel currents from cell-attached patches were investigated. 2. Cells had a mean resting potential of -38 mV and mean input resistance of 1.6 G omega. Single action potentials were evoked under current clamp during the injection of depolarizing currents. 3. A voltage-dependent inward sodium current was observed which reversed at +44 mV. A Boltzmann fit to the activation curve gave a half-maximal activation voltage of -41.6 mV and a 'slope' of 3.9 mV. The steady-state inactivation curve had a half-maximal inactivation voltage of -81 mV and a 'slope' of 9.7 mV. 4. The time-dependent activation and inactivation of the current displayed classical Hodgkin-Huxley kinetics. Values for the time constants tau m and tau h of 0.16 and 0.63 ms were calculated for a voltage jump from -80 to -10 mV; tau m and tau h decreased as the step potential was changed from -30 to +20 mV. 5. Outward currents were activated in bathing solutions substantially free of anions and could thus be attributed to potassium ions. The tail current reversed in direction on repolarization to -60 mV when the potassium concentration in the bathing solution was increased from 6 to 30 mM. When the bathing solution contained 145 mM-potassium, and the patch pipette, 95 mM, a depolarization to -10 mV from a holding potential of -60 mV evoked an inward current. 6. Outward currents were examined by using voltage pulses which depolarized the cell to -20 mV, or more positive values, from a holding potential of -80 mV and by pulses which depolarized the cell to 0 mV, or to positive values, from a holding potential of -30 mV. A Boltzmann fit of typical activation data gave a half-maximal activation voltage of 17 mV and a 'slope' of 14 mV. 7. The time course of the rising phase of the current was described by a function of the form A(1-exp[-(t-delta t)/tau]), where delta t varied between 1 and 4 ms and tau varied between 4 and 27 ms, decreasing with increasing depolarization. There was no evidence for a fast transient component. 8. The amplitude of outward currents was reduced by extracellular calcium ions, cobalt ions, tetraethylammonium and 4-aminopyridine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the sodium and potassium currents of a human neuroblastoma cell line. 202 15

The average concentration of sodium is known to be elevated in some tumors relative to normal tissues, and necrosis is suspected of being a possible cause. We have performed in vivo sodium-23 magnetic resonance imaging (MRI) of IMR-5 neuroblastoma in the athymic nude mouse on a 1.9-Tesla, small-bore animal imaging system. We compared the sodium images with histologic analysis for necrosis and with proton images, chemical measurements of water and blood content, and sodium and potassium concentrations. We found that the sodium concentrations determined by MRI were proportional to the fraction of the tumor tissue that was necrotic. Correlation coefficients varied from 0.65 to 0.78, depending upon how the data were selected. With further refinement it is possible that the sodium concentration measurements determined noninvasively by MRI may have applications as part of clinical diagnosis and staging of soft tissue tumors.
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PMID:Sodium nuclear magnetic resonance imaging of neuroblastoma in the nude mouse. 205 28

Cellular electrophysiologic responses to serotonin and serotonin agonists in vertebrate neurons and cell cultures derived from neuronal or neuroblastoma x glioma hybrids are reviewed. Emphasis is on local rather than systemic drug administration, and on intracellular and patch clamp recording. Activation of serotonin receptors can open and close potassium channels, reduce voltage-dependent calcium currents and calcium-activated potassium currents, enhance hyperpolarization-activated cation currents, and open ligand-gated cation channels. The pharmacology of these responses is described and the assignment of serotonin receptor subtypes discussed. The review is selective rather than inclusive and was concluded in November 1989.
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PMID:Electrophysiologic studies of serotonin receptor activation. Answered and unanswered questions. 207 78

In this study, hepatic microsomes from 5,6-benzoflavone induced C57BL/10 mice were used. To inhibit monooxygenase activities, the monoclonal antibody MAb 1-7-1 recognizing two isoenzymes of methylcholanthrene-induced cytochrome P-450 was applied. Microsomes were incubated with tritium labeled benzo(a)pyrene [G-3H]BP for 10 min at 37 degrees C. The incubation mixture contained: 50 mM potassium phosphate buffer, pH 7.25; 30 mM KCl; 3 mM MgCl2; 2 mM NADPH; 80 microM [G-3H]BP (specific activity 50 mCi/mmol); and monoclonal antibody MAb 1-7-1 or ascites fluid (NBS) containing nonspecific IgG as a control. The ratio of antibody protein/microsomal protein was 2:5. BP metabolites were extracted from incubation mixtures by ethyl acetate. The organic layer was dried over sodium sulfate, and evaporated under a stream of nitrogen. To separate BP metabolites HPLC technology was used. The column was eluted with methanol gradient (60-100%) for 45 minutes. The radio-activity of collected samples was determined using liquid scintillation counter. Differential inhibitory effects of MAb 1-7-1 on BP-metabolites formation were found, e.g. 7,8-diol was inhibited by 86.1% and quinones by 62.5%. The predominant metabolite, 3-OH-BP, was inhibited by 80.4%. Moreover, it was found that MAb 1-7-1 inhibition of benzo(a)pyrene hydroxylase activity (by 75.8%, as measured by fluorescent technique) was very similar to the inhibition of 3-OH-BP along with 9-OH-BP formation (as measured by HPLC).
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PMID:[Effect of monoclonal antibody against methylcholanthrene-induced cytochrome P-450 forms on benzo(a)pyrene metabolism in hepatic microsomes of C57BL/10 mice]. 209 79

External application of bradykinin (BK) to mouse neuroblastoma X mouse fibroblast hybrid NL308 cells and mouse neuroblastoma X rat glioma hybrid NG108-15 cells produced a transient outward (hyperpolarizing) current. In NG108-15 cells, BK also induced an inward (depolarizing) current associated with a decrease in input membrane conductance, which results from the inhibition of a voltage-sensitive potassium current, the M-current. However, in NL308 cells, either no depolarization was elicited by BK or, even if the BK-induced depolarization was evoked, it was associated with an increased conductance. To explain the above difference, the intracellular second messenger system of NL308 cells was examined in detail. BK induced the rapid accumulation (three- to fivefold higher than the control level) of inositol 1,4,5-trisphosphate (InsP3) in NL308 cells. The cytosolic Ca2+ concentration was also elevated to 540 nM from 180 nM at a basal level. This seems to be enough to activate a voltage-independent and Ca2(+)-sensitive K+ current, resulting in the hyperpolarization. Intracellular injection of InsP3 replicated the hyperpolarization. NL308 cells possess protein kinase C (C-kinase), with specific activities of C-kinase in cytosolic and membrane fractions being 233 and 24 pmol/min/mg protein, respectively. The activity associated with particulates became higher after phorbol dibutyrate (PDBu) treatment. But NL308 cells did not show the characteristic inward relaxation by step hyperpolarizations and the outward rectification in the current-voltage relationship, indicating that the M current is deficient in NL308 cells. Therefore, application of PDBu failed to mimic the inward current. The results suggest the role of InsP3 and C-kinase in controlling two K+ currents.
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PMID:Bradykinin induces inositol 1,4,5-trisphosphate-dependent hyperpolarization in K+ M-current-deficient hybrid NL308 cells: comparison with NG108-15 neuroblastoma x glioma hybrid cells. 213 30

The effects of chloramine-T (CL-T) on voltage-dependent potassium channels in neuroblastoma cells were analysed using the whole-cell current recording technique. CL-T irreversibly decreased the peak whole-cell K current, considerably slowed its inactivation and shifted its activation-voltage curve towards positive voltages by 6 mV. Under control conditions, the inactivation of the whole-cell K current could be described by the sum of two exponentials, F and S, whose time constants at +50 mV were tau F = 1.00 +/- 0.15 S and tau S = 5.72 +/- 0.47 S respectively. After CL-T, it could be described by the sum of two (S1 and S2) or three (F, S1 and S2) exponentials whose time constants at +50 mV were: tau F = 0.81 +/- 0.22 S, tau S1 = 6.46 +/- 0.60 S and tau S2 = 48.56 +/- 3.64 S. Under control conditions, F and S inactivating components of the whole-cell K current were blocked by 4-aminopyridine, with a Hill coefficient of 1 and apparent dissociation constants of 0.04 and 0.7 mM respectively. After CL-T, both S1 and S2 components were equally blocked by 4-aminopyridine with a Hill coefficient of 0.25, being reduced to 64% of their control values by 10 mM. CL-T is known to slow the inactivation of sodium channels and to oxidize sulphydryl amino acids and unsaturated lipids. It is concluded that the inactivation gates of voltage-dependent sodium and potassium channels are either constituted of the same amino acid residues or are controlled by unsaturated lipid surrounding or bound to the channel proteins.
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PMID:Modification of electrophysiological and pharmacological properties of K channels in neuroblastoma cells induced by the oxidant chloramine-T. 216 42


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