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

Using radioreceptor assay techniques to measure the kinetics of GABA and diazepam receptors, a relationship between GABA and benzodiazepine receptors has been firmly established in membranes of brain and neuroblastoma NB2a clonal cell lines. Occupancy of benzodiazepine receptors uncovers a new population of GABA receptors (GABA2 receptors) endowed with high affinity for GABA. Moreover, stimulation of GABA receptors increases the affinity of 1,4-benzodiazepine receptors for 1,4-benzodiazepines. This reciprocal interaction appears to be mediated by an endogenous regulatory protein (for details on this protein see [14 and 29]) which allosterically regulates GABA2 receptors while it competitively interacts with benzodiazepines for their specific binding sites. The rank order of potency of the various 1,4-benzodiazepines to block the action of this protein inhibitor on GABA receptors is related to their capacity to displace 3H-diazepam binding. These data suggest that the interaction between the 1,4-benzodiazepine receptors and the endogenous protein modulator of GABA2 receptors might play a role in the pharmacological action of the 1,4-benzodiazepines.
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PMID:Molecular mechanisms regulating the interactions between the benzodazepines and GABA receptors in the central nervous system. 4 Feb 54

The effect of sodium n dipropylacetate (nDPA), a competitive GABA-T inhibitor with respect to GABA, has been investigated on glial and neuronal cellular GABA level. After 1 to 4 days incubation with nDPA in the culture medium, a decrease of GABA level in M5 neuroblastoma clonal cell lines and no modification of GABA level in C6 astrocytoma cells has been observed. The combined addition of nDPA 4 micrometer with dibutyryl cyclic AMP (1 mM) to the culture medium induces the same decrease in GABA level in C6 astrocytoma cells as the addition of DB-c-AMP alone. After shorter incubation time with nDPA (5-150 min), we observed a decreased GABA level in C6 astrocytoma glial cells.
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PMID:[Effect of sodium n-dipropylacetate (sodium valproate) on GABA level of neuronal and glial cells in culture]. 21

Both glial and neuronal cells maintained in primary culture were found to accumulate [3H]GABA by an efficient "high-affinity" uptake system (apparent Km = 9 muM, Vmax = 0.018 and 0.584 nmol/mg/min, respectively) which required sodium ions and was inhibited by 1 mM ouabain. Strychnine and parachloromercuriphenylsulfonate (pCS) (both at 1mM) also strongly inhibited uptake of [3H]GABA, but metabolic inhibitors (2,4-dinitrophenol, potassium cyanide, and malonate) were without effect. Only three structural analogs of GABA (nipecotate, beta-alanine, and 2,4-diaminobutyrate) inhibited uptake of [3H]GABA, while several other compounds with structural similarities to GABA (e.g. glycine, L-proline, and taurine) did not interact with the system. The kinetic studies indicated presence of a second uptake (Km = 92 muM, Vmax = 0.124 nmol/mg/min) in the primary cultures containing predominantly glioblasts. On the other hand, only one of the neuronal cell lines transformed by simian virus SV40 appeared to accumulate [3H]GABA against a concentration gradient. Apparent Km of this uptake was relatively high (819 muM), and it was only weakly inhibited by 1 mM ouabain and 1 mM pCS. The structural specificity also differed from that of the uptake observed in the primary cultures. Significantly, non of the nontransformed continuous cell lines of either tumoral (glioma, C6; neuroblastoma, M1; M1NN) or normal (NN;I6) origin actively accumulated [3H]GABA. It is suggested that for the neurochemical studies related to GABA and requiring homogeneous cell populations, the primary cultures offer a better experimental model than the continuous cell lines.
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PMID:High-affinity uptake of gamma-aminobutyric acid in cultured glial and neuronal cells. 22 77

1. Some possible molecular mechanisms of action of the anxiolytic, anticonvulsant and neuroprotective agent MK-801 have been examined in 'whole-cell' voltage clamp recordings performed on rat hippocampal and cortical neurones, bovine adrenomedullary chromaffin cells and N1E-115 neuroblastoma cells maintained in cell culture. 2. Transmembrane currents recorded from rat hippocampal and cortical neurones in response to locally applied N-methyl-D-aspartate (NMDA) were antagonized by MK-801 (0.1-3.0 microM). Blockade was use-dependent, and little influenced by transmembrane potential. MK-801 (3 microM) had no effect on currents evoked by kainate (100 microM). 3. The antagonism of NMDA-induced currents by MK-801 was only slowly and incompletely reversed when the cell membrane potential was clamped at -60 mV during washout. Prolonged applications of NMDA at +40, but not -60 mV during washout, markedly accelerated recovery from block. 4. In contrast to MK-801, ketamine (10 microM) blocked NMDA-induced currents in a voltage-dependent manner. Blockade increased with membrane hyperpolarization and was completely reversible upon washout. 5. MK-801 (1-10 microM) produced a voltage- and concentration-dependent block of membrane currents elicited by ionophoretically applied acetylcholine (ACh) recorded from bovine chromaffin cells. The block was readily reversible upon washout. 6. gamma-Aminobutyric acidA (GABAA) receptor-mediated chloride currents of chromaffin cells were unaffected by MK-801 (1-100 microM). In contrast, such currents were potentiated by diazepam (1 microM). MK-801 (100 microM) had no effect on currents evoked by GABA on hippocampal neurones. 7. MK-801 (10 microM) had little effect on membrane currents recorded from N1E-115 neuroblastoma cells in response to ionophoretically applied 5-hydroxytryptamine (5-HT). Such currents were antagonized by the 5-HT3 receptor antagonist GR 38032F (1 nM) and also by MK-801 at high concentration (100 microM). 8. Voltage-activated, tetrodotoxin-sensitive, sodium currents of chromaffin cells were unaffected by 10 microM MK-801. However, at a relatively high concentration (100 microM), MK-801 reduced the amplitude of such currents to approximately 77% of control. 9. The relevance of the present results to the central actions of MK-801 is discussed.
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PMID:The mechanism of action and pharmacological specificity of the anticonvulsant NMDA antagonist MK-801: a voltage clamp study on neuronal cells in culture. 264 6

Benzodiazepines have been shown to change the turnover rate of 5-HT, ACh and catecholamines stored in selected brain areas, but the doses required for these effects are several-fold higher than those which elicit a persistent punished behavior or antagonize isoniazid, bicuculline or picrotoxin convulsion. The selective antagonism against convulsions elicited by drugs that impair GABAergic transmission, the capability of muscimol and other GABA receptors agonists to mimic behavioral and anticonvulsant action of the benzodiazepines have suggested that benzodiazepines facilitate GABA transmission. This facilitation of the GABA tranmission is due to an allosteric facilitation of high-affinity GABA binding to postsynaptic receptors. Also, the high-affinity binding of the benzodiazepines can be facilitated by GABA mimetics. Endogenous inhibitors of the benzodiazepines and GABA binding extracted from synaptic membranes play a role in facilitating these interactions. Using neuroblastoma 2A cells as a model and Cl- influx as an index of GABA receptor activation, it will be shown that the benzodiazepines facilitates not only GABA binding but also its action on Cl- channels. Also, glioma C6 cells have high affinity receptors for GABA and benzodiazepine binding but these binding sites are not linked to a Cl- channel. It is concluded that the benzodiazepines displace a regulatory protein for high-affinity GABA receptors and thereby facilitate GABAergic transmission.
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PMID:Benzodiazepines and neurotransmitters. 610 85

Strain N2a neuroblastoma cells were grown in monolayer and in spinner culture in Coon's modified Hamms F12 medium, or in Dulbecco's modified Eagle Medium with either high (4.5 g/l) or low (1.0 g/l) glucose, and the specific binding of [3H]GABA and [3H]flunitrazepam were determined. GABA binding was highest in monolayer cells grown in low glucose Dulbecco's, and undetectable in monolayer or spinner cells grown in high glucose Dulbecco's. Binding of flunitrazepam was not sensitive to the medium or culture conditions. Flunitrazepam binding suggested the presence of a 'peripheral' benzodiazepine receptor, because: (a) binding was blocked by RO5-4864 but not clonazepam; (b) binding was not enhanced by 0.1 mM GABA or 50 mM Cl-; and (c) the Kd value was approximately 300 nM. Neither ethanol (100 mM) nor pentobarbital (0.2 mM) had any effect on the binding of GABA; flunitrazepam binding was not affected by ethanol but was decreased about 20% by pentobarbital. GABA, muscimol and veratridine did not alter the membrane potential of the cells, as measured by tetraphenylphosphonium accumulation. The data are discussed in terms of separate receptors for GABA and for benzodiazepines which are not incorporated into a GABA--benzodiazepine receptor--chloride ionophore complex.
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PMID:GABA and flunitrazepam binding to neuroblastoma cell membranes--effects of growth conditions, ethanol and pentobarbital. 612 16

The kinetics of mutual inhibition of taurine and hypotaurine uptake were studied using neuroblastoma C1300 cells as neuronal model. Hypotaurine and GABA inhibited taurine uptake competitively, increasing the apparent Km. High-affinity uptake of hypotaurine was completely abolished and the low-affinity component competitively inhibited by taurine. GABA affected noncompetitively low-affinity hypotaurine uptake, whereas the effect on high-affinity uptake was competitive, with an increase in the apparent Km. All structural analogues tested inhibited taurine and hypotaurine uptakes similarly. The most potent inhibitors were beta-alanine and 2-guanidinoethanesulphonic acid. The mutual inhibition and similar specificity profiles of taurine and hypotaurine uptakes showed that these amino acids employ a single transport system in neuroblastoma cells. Competitive inhibition by GABA of the high-affinity uptake of taurine and hypotaurine further suggests that also GABA uses the same carrier system.
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PMID:Taurine and hypotaurine transport by a single system in cultured neuroblastoma cells. 651 87

Sodium bromide was applied in vitro to mouse neuroblastoma cells of different ages for short and long periods (2 h to 10 days). The changes observed light-and-electron microscopically were similar to those described earlier after GABA treatment. Coated vesicles proliferated and originated by pinching off from the Golgi complex and from the rough endoplasmic reticulum. Numerous coated vesicles were continuous with the plasma membrane, especially near zones in which electron-dense material aggregated at the inner aspect of the plasmalemma. Small invaginations, similar in ultrastructure to coated vesicles, were also formed. It is unclear whether the coated vesicles or the dense plasmalemma invaginations contribute to the "undercoating" by fusing with the adjacent electron-dense plasma membrane. There was a distinct increase in the number and area of specialized contacts (intermediate junctions and zonulae adhaerentes) between cells and their processes. A floccular or filamentous electron-dense substance varying in amount and appearance was occasionally seen between the contacting membranes. Varicosities of terminal swellings of cell processes contained vesicles of variable size, shape and density, and also profiles of the smooth endoplasmic reticulum. Under the influence of sodium bromide, similar to the effect of GABA, mitochondria appeared within the varicosities, and primitive contacts (intermediate junctions) were formed between the terminal swellings and potential postsynaptic elements, which were absent in controls. Additionally, dense-core vesicles proliferated and aggregated at the cell periphery. They were often arranged linearly below the plasma membranes of perikarya and processes, and surrounded by a highly electron-dense substance. The similarity of the present findings to those obtained after GABA treatment and their relation to synaptogenesis are discussed.
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PMID:Morphological changes induced by sodium bromide in murine neuroblastoma cells in vitro. 708 7

Isogabaculine (3-amino-1,3-cyclohexadienyl carboxylic acid; RMI 71,932), an irreversible inhibitor of GABA transaminase, when added to mouse neuroblastoma cells in spinner culture at the time of induction of cell proliferation, increased ornithine decarboxylase (ODC) activity threefold above that of normal control cells and twofold above that of GABA (gamma-aminobutyric acid)-treated cells. Isogabaculine did not affect ODC activity of rat glioma (C6) or rat hepatoma (HTC) cells. As determined by half-life measurements of ODC and intracellular GABA concentrations, isogabaculine apparently has a direct stabilizing effect on ODC in neuroblastoma cells that is unrelated to the accumulation of GABA due to GABA transaminase inhibition. Putrescine metabolism to GABA or spermidine was determined in C6, HTC, and neuroblastoma cells in the presence or absence of isogabaculine and/or GABA. Neither GABA nor isogabaculine treatment dramatically altered the metabolism of putrescine to GABA or spermidine in neuroblastoma, C6 glioma, or HTC cells. However, the appreciable amount of labeled GABA formed from putrescine indicated that this metabolic route may be more important than was previously thought.
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PMID:Effect of GABA and isogabaculine on ornithine decarboxylase and putrescine metabolism. 709 60

(Gamma aminobutyric acid) GABA was applied to cultures of mouse neuroblastoma cells of different ages at concentrations ranging from 10(-4) to 10(-6) M. The cultures were exposed to GABA either in short term experiments for 2 h to 2 days or for longer periods by adding the substance twice within 10 days at 5-day intervals. The following effects were observed: (1) There was a strong proliferation of coated vesicles, appearing to derive from the Golgi complex and the rough endoplasmic reticulum (RER), and also showing all intermediate stages of fusion and pinching off from the plasma membranes. (2) In numerous areas, electron-dense material aggregated at the inner aspect of the plasma membrane and around small invaginations of the plasmalemma. (3) The number and area of specialized contacts increased between cells and their processes. (4) Similar to cultures free of GABA, varicosities and terminal swellings of the cells and their processes were filled with small round vesicle, 40--60 nm in diameter, or with smooth, very large, empty-appearing vesicular inclusions, or with flat pleiomorphic vesicles. In addition, mitochondria and some formations of the smooth endoplasmic reticulum (SER) appeared, and primitive contacts (symmetrical densities) were formed. (5) Dense-cored vesicles were found peripherally and linearly arranged, surrounded by an electron-dense substance. (6) Electron-dense material of unknown origin was seen between cells or their processes near the peripherally arranged dense-cored vesicles. Exogenous GABA may play a specific role in the early stages of synaptogenesis, since it showed a positive effect on the neuroblastoma cells, which in the absence of GABA are only capable of forming primitive or immature presynaptic elements. The significance of the peripheral accumulation of dense-cored vesicles, accompanied by an amorphous, electron-dense substance occurring both intra- and extracellularly is discussed.
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PMID:Effect of GABA-administration on murine neuroblastoma cells in culture. I. Increased membrane dynamics and formation of specialized contacts. 726 Oct 42


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