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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apart from being a prominent (inhibitory) neurotransmitter that is widely distributed in the central and peripheral nervous system, gamma-aminobutyric acid (GABA) has turned out to exert trophic actions. In this manner GABA may modulate the neuroplastic capacity of neurons and neuron-like cells under various conditions in situ and in vitro. In the superior cervical ganglion (SCG) of adult rat, GABA induces the formation of free postsynaptic-like densities on the dendrites of principal neurons and enables implanted foreign (cholinergic) nerves to establish functional synaptic contacts, even while preexisting connections of the preganglionic axons persist. Apart from postsynaptic effects, GABA inhibits acetylcholine release from preganglionic nerve terminals and changes, at least transiently, the neurochemical markers of cholinergic innervation (acetylcholinesterase and nicotinic receptors). In murine neuroblastoma cells in vitro, GABA induces electron microscopic changes, which are similar in principle to those seen in the SCG. Both neuroplastic effects of GABA, in situ and in vitro, could be mimicked by sodium bromide, a hyperpolarizing agent. In addition, evidence is available that GABA via A- and/or B-receptors may exert direct trophic actions. The regulation of both types of trophic actions (direct, receptor-mediated vs. indirect, bioelectric activity dependent) is discussed.
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PMID:Modulation by GABA of neuroplasticity in the central and peripheral nervous system. 847 68

Cell culture techniques, high-resolution in vitro 1H NMR spectroscopy, and chromatographic analyses were used to compare the properties of three types of human brain and nervous system tumours. Cell lines were immunocytochemically characterized at all stages in culture with specific antibodies. Intracellular metabolites present in cell extracts were analysed by 1H NMR spectroscopy and by high performance liquid chromatography (HPLC). The spectra from meningiomas, neuroblastomas, and glioblastomas displayed, in addition to similarities-including the presence of signals from leucine, isoleucine, valine, threonine, lactate, acetate, glutamate, choline-containing compounds and glycine-certain distinguishing metabolic features. Spectra from meningiomas featured relatively high signals from alanine. Intense signals from creatine were present in neuroblastoma spectra, while in spectra from glioblastoma they were not detectable. We found statistically significant differences by 1H NMR spectroscopy in the amounts of alanine, glutamate, creatine, phosphorylcholine and threonine among the types of tumours examined. HPLC determinations confirmed that there were also other metabolites specific to a type of tumour, such as taurine, gamma-aminobutyric acid, and serine. We suggest that these findings have potential relevance for the development of non-invasive diagnosis of tumour lineage by 1H NMR spectroscopy in vivo.
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PMID:Characteristic metabolic profiles revealed by 1H NMR spectroscopy for three types of human brain and nervous system tumours. 873 81

Neuroactive steroids rapidly alter neuronal excitability through their action via the cell surface. The 3 alpha-hydroxy ring A-reduced pregnane steroids enhance gamma-aminobutyric acid (GABA)-mediated Cl- currents while pregnenolone sulfate and dehydroepiandrosterone sulfate may exert functional antagonistic properties. Based on our previous findings that the 3 alpha-hydroxy ring A-reduced pregnane steroids allotetrahydroprogesterone and allotetrahydrodeoxycorticosterone may regulate gene expression via the progesterone receptor after intracellular oxidation, we have characterized the effects of a series of natural and synthetic neuroactive steroids at the genomic level using a cotransfection system with various steroid receptor expression vectors and a reporter gene in a human neuroblastoma cell line. Pregnanolone and pregnenolone were able to activate both the chicken and the human progesterone receptor while the synthetic 3 alpha-hydroxylated derivative alphaxalone and dehydroepiandrosterone were active via the chicken progesterone receptor but devoid of transcriptional activity via the human progesterone receptor. Moreover, the antiglucocorticoid activity of dehydroepiandrosterone reported at the systemic level could not be reconstituted in the cellular cotransfection system. None of the neuroactive steroids bound directly to steroid receptors. Thus, their genomic activity appears to be mediated via intracellular metabolization. This study provides evidence for differential genomic effects of neuroactive steroids in a structure-specific and species-specific way that may have impact on the development of these steroids for therapeutic application.
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PMID:Steroid receptor-mediated effects of neuroactive steroids: characterization of structure-activity relationship. 881 74

This study compared the interaction between ethanol and gamma-aminobutyric acid (GABA)-mediated current responses elicited in several immortalized cell lines and stably transfected cells, as well as in cultured and acutely dissociated rat cerebellar Purkinje cells. Only cell lines that were found previously to possess functional GABAA receptors were examined in this study. Under identical recording conditions, ethanol (10-200 mM) exerted no effect on GABA-induced currents in any of the cell lines or stably transfected cells tested in this study. However, GABA responses monitored in both primary culture and acutely dissociated Purkinje cells were significantly potentiated by ethanol (25 and 50 mM). Mouse pancreatic cells (RINm5F) were insensitive to both diazepam and ethanol suggesting the expression of a GABAA receptor isoform lacking a gamma subunit. Immortalized neuroblastoma IMR-32 cells displayed GABA responses that could be distinguished based on differential sensitivity to diazepam. However, none of the IMR-32 cells displayed GABA responses that were sensitive to modulation by ethanol. GABA responses in the stably transfected cell lines, PA3 (alpha1beta1gamma2L) and WSS-1 (alpha1beta2gamma2), were also unaffected by exposure to ethanol. In Purkinje cells acutely dissociated from the neonatal cerebellum, the ethanol-induced potentiation of GABA-induced current response could be observed before postnatal day 7, when only the gamma2S but not the gamma2L splice variant is expressed. This indicates that the gamma2L subunit is not necessary for an ethanol-induced potentiation of GABAA receptor-mediated response to become manifest. In addition, the results point to inherent differences that should be taken into account in interpreting comparative data between native and recombinant GABAA receptors.
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PMID:Ethanol-GABAA receptor interactions: a comparison between cell lines and cerebellar Purkinje cells. 945 26

Cell lines are commonly used for studying recombinant heterooligomeric ion channels with defined subunit composition. Such studies often ignore the contribution of endogenous proteins in the assembly of mature channels. We examined whether an endogenous subunit was required for the functional expression of gamma-aminobutyric acid type A (GABA(A)) receptors in WSS-1 cells, HEK293 cells stably expressing recombinant alpha1 and gamma2 subunits. Our pharmacological and RT-PCR analyses of GABA(A) receptors and their mRNAs in WSS-1 cells confirm the presence of alpha1 and gamma2 subunits and suggest the existence of an endogenous beta3 subunit. Whole-cell GABA-evoked currents recorded from untransfected WSS-1 cells were blocked by bicuculline methiodide and enhanced by anesthetics and anticonvulsants including the subunit-selective compounds diazepam and loreclezole. These data suggest that, in addition to the gamma2 subunit, WSS-1 cell receptors also contain beta2/3 subunits. RT-PCR revealed that WSS-1 cells and parental HEK293 cells contain beta3 mRNA. We examined the contribution of the beta3 subunit in the function of receptors formed by expression of alpha1 and gamma2S subunits. Untransfected HEK293 cells were unresponsive to GABA. Cells transfected with alpha1 and gamma2S cDNAs displayed small diazepam and loreclezole responsive GABA-activated currents. By contrast, the expression of alpha1 and gamma2S cDNAs in the neuroblastoma NB41A3 cell line, that lacks beta subunit mRNAs, failed to produce functional receptors. These data reaffirm that alpha1 and gamma2S subunits alone do not form functional GABA(A) receptors and that receptors of WSS-1 cells contain alpha1, beta3 and gamma2S subunits.
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PMID:The influence of an endogenous beta3 subunit on recombinant GABA(A) receptor assembly and pharmacology in WSS-1 cells and transiently transfected HEK293 cells. 1072 82

delta-Hexachlorocyclohexane (delta-HCH), a lipophilic neurodepressant agent, has been shown to inhibit neurotransmitter release and stimulate ryanodine-sensitive Ca(2+) channels. However, the effect of delta-HCH on neuronal activity remains unclear, although it may enhance the gamma-aminobutyric acid-induced current. Its effects on ionic currents were investigated in rat pituitary GH(3) cells and human neuroblastoma IMR-32 cells. In GH(3) cells, delta-HCH increased the amplitude of Ca(2+)-activated K(+) current (I(K(Ca))). delta-HCH (100 microM) slightly inhibited the amplitude of voltage-dependent K(+) current. delta-HCH (30 microM) suppressed voltage-dependent L-type Ca(2+) current (I(Ca, L)), whereas gamma-HCH (30 microM) had no effect on I(Ca, L). In the inside-out configuration, delta-HCH applied intracellularly did not change the single channel conductance of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels; however, it did increase the channel activity. The delta-HCH-mediated increase in the channel activity is mainly mediated by its increase in the number of long-lived openings. delta-HCH reversibly increased the activity of BK(Ca) channels in a concentration-dependent manner with an EC(50) value of 20 microM. delta-HCH also caused a left shift in the midpoint for the voltage-dependent opening. In contrast, gamma-HCH (30 microM) suppressed the activity of BK(Ca) channels. Under the current-clamp mode, delta-HCH (30 microM) reduced the firing rate of spontaneous action potentials; however, gamma-HCH (30 microM) increased it. In neuroblastoma IMR-32 cells, delta-HCH also increased the amplitude of I(K(Ca)) and stimulated the activity of intermediate-conductance K(Ca) channels. This study provides evidence that delta-HCH is an opener of K(Ca) channels. The effects of delta-HCH on these channels may partially, if not entirely, be responsible for the underlying cellular mechanisms by which delta-HCH affects neuronal or neuroendocrine function.
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PMID:Stimulatory effects of delta-hexachlorocyclohexane on Ca(2+)-activated K(+) currents in GH(3) lactotrophs. 1077 68

The gamma-aminobutyric acid (GABA) response profiles of IMR-32 human neuroblastoma cells were examined using whole-cell patch clamp and RT-PCR techniques. GABA activated a concentration-dependent and bicuculline-sensitive current, and RT-PCR revealed the expression of multiple GABA(A) receptor subunit mRNAs (alpha(1), alpha(3), alpha(4), beta(1), beta(3), gamma(2), and delta). A pharmacological profile of the GABA-induced current was derived using several subunit-selective agents. Diazepam, which requires the presence of a gamma subunit in order to modulate GABA(A) receptor-mediated responses, potentiated GABA-induced currents in a subset of IMR-32 cells. Two populations of GABA-activated currents were also evident based on sensitivity to modulation by zinc. Comparison of zinc- and diazepam-induced modulation of GABA-induced current responses in the same cells revealed an inverse correlation between these two modulators. No differences, however, were observed with the GABA(A) receptor modulators loreclezole, allopregnanolone, and pentobarbital. Thus, IMR-32 cells maintained in culture are heterogeneous in terms of expression of GABA(A) receptor isoforms.
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PMID:Heterogeneity of GABA(A) receptor-mediated responses in the human IMR-32 neuroblastoma cell line. 1079 53

1. Using pharmacological analysis and fura-2 spectrofluorimetry, we examined the effects of gamma-aminobutyric acid (GABA) and related substances on intracellular Ca(2+) concentration ([Ca(2+)]i) of hybrid neurones, called MD3 cells. The cell line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal root ganglion (DRG) neurone. 2. MD3 cells exhibited DRG neurone-like properties, such as immunoreactivity to microtubule-associated protein-2 and neurofilament proteins. Bath applications of capsaicin and alpha, beta-methylene adenosine triphosphate reversibly increased [Ca(2+)]i. However, repeated applications of capsaicin were much less effective. 3. Pressure applications of GABA (100 microM), (Z)-3-[(aminoiminomethyl) thio] prop-2-enoic acid sulphate (ZAPA; 100 microM), an agonist at low affinity GABA(A)-receptors, or KCl (25 mM), transiently increased [Ca(2+)]i. 4. Bath application of bicuculline (100 nM - 100 microM), but not picrotoxinin (10 - 25 microM), antagonized GABA-induced increases in [Ca(2+)]i in a concentration-dependent manner (IC(50)=9.3 microM). 5. Ca(2+)-free perfusion reversibly abolished GABA-evoked increases in [Ca(2+)]i. Nifedipine and nimodipine eliminated GABA-evoked increases in [Ca(2+)]i. These results imply GABA response dependence on extracellular Ca(2+). 6. Baclofen (500 nM - 100 microM) activation of GABA(B)-receptors reversibly attenuated KCl-induced increases in [Ca(2+)]i in a concentration-dependent manner (EC(50)=1.8 microM). 2-hydroxy-saclofen (1 - 20 microM) antagonized the baclofen-depression of the KCl-induced increase in [Ca(2+)]i. 7. In conclusion, GABA(A)-receptor activation had effects similar to depolarization by high external K(+), initiating Ca(2+) influx through high voltage-activated channels, thereby transiently elevating [Ca(2+)]i. GABA(B)-receptor activation reduced Ca(2+) influx evoked by depolarization, possibly at Ca(2+)-channel sites in MD3 cells.
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PMID:Analysis of GABA(A)- and GABA(B)-receptor mediated effects on intracellular Ca(2+) in DRG hybrid neurones. 1152 1

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.
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PMID:Neuroprotective actions of pyridoxine. 1268 37

Effects of the neurotoxic organic solvent toluene on human neuronal nicotinic acetylcholine (nACh) and gamma-aminobutyric acid type A (GABA(A)) neurotransmitter receptors were investigated in whole-cell voltage-clamped IMR-32 neuroblastoma cells. Ion currents evoked by near maximum effective concentrations of 1 mM acetylcholine (ACh) and 1 mM gamma-aminobutyric acid (GABA) are inhibited by toluene in a concentration-dependent way. Concentration-effect curves of toluene yield IC(50) values of 276+/-26 and 39+/-6 microM and slope factors of 1.4+/-0.2 and 0.8+/-0.1 for inhibition of the ACh- and GABA-induced ion currents, respectively. The results demonstrate the selective inhibition of human GABA(A) receptors by toluene at concentrations comparable with brain concentrations associated with occupational exposure.
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PMID:Selective inhibition of gamma-aminobutyric acid type A receptors in human IMR-32 cells by low concentrations of toluene. 1292 78


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