Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the neuroblastoma X glioma hybrid cell line NG108-15, bradykinin (BK) receptor stimulation induced a rapid and concentration-dependent rise in cytosolic free Ca2+ levels, as measured with the Ca2(+)-sensitive fluorescent dye fura-2. The Ca2+ transient was present in the absence of extracellular Ca2+ and was associated with a concentration-dependent production of inositol phosphates, particularly inositol trisphosphate (InsP3). Pretreatment of intact NG108-15 cells with forskolin or dibutyryl-cAMP plus isobutylmethylxanthine reduced BK-stimulated InsP3 production and the increase in cytosolic free Ca2+. Membranes prepared from forskolin- and [3H]inositol-pretreated NG108-15 cells also showed a diminished production of InsP3 elicited by guanosine 5'-[gamma-thio]triphosphate, NaF, or BK plus GTP. On the other hand, the Ca2+ sensitivity of membrane-associated phosphoinositide-specific phospholipase C (PI-PLC) was unaffected by forskolin pretreatment of intact NG108-15 cells. Collectively, these results suggest that A-kinase may inhibit receptor-mediated and postreceptor stimulation of PI-PLC in neuron-like cells, perhaps by impairing the coupling between a guanine nucleotide-binding protein and PI-PLC.
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PMID:Cyclic AMP inhibits inositol polyphosphate production and calcium mobilization in neuroblastoma X glioma NG108-15 cells. 216 7

Membrane depolarization is a critical component of neural signaling; in recent years there also has been a great deal of evidence that membrane depolarization can regulate neural gene expression. Therefore, excitatory neurotransmission may be an important mechanism of neural plasticity. We have investigated the intracellular pathways and DNA regulatory elements through which membrane depolarization activates expression of the neural gene encoding human proenkephalin. In PC12 and C6-glioma cells, depolarization-induced expression of a transfected proenkephalin fusion gene was proportional to extracellular calcium concentration and was inhibited by verapamil. Activation of the gene by KCl-induced depolarization or the calcium ionophore A23187 was dependent upon and synergistic with cAMP in PC12 and C6-glioma cells, but neither depolarization nor treatment with A23187 affected cAMP levels. Trifluoperazine and W7 inhibited depolarization-induced gene expression but did not affect expression induced by the adenylyl cyclase activator forskolin. At the level of the DNA, depolarization-induced activation is conferred on the proenkephalin gene by a previously characterized cAMP-inducible enhancer. Multiple copies of a single component element of that enhancer, containing the CGTCA sequence motif characteristic of cAMP regulatory elements, can reconstitute the entire repertoire of responses to both cAMP and depolarization. These data suggest a model in which membrane depolarization activates gene expression through a calcium-dependent pathway, potentially involving calmodulin, and in which the transcriptional responses to both cAMP and calcium are transduced by the same DNA element.
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PMID:The effect of depolarization on expression of the human proenkephalin gene is synergistic with cAMP and dependent upon a cAMP-inducible enhancer. 216 56

Ethanol has been shown to suppress calcium uptake into depolarized synaptosomes, to reduce the durations of calcium spikes in cultured cells and to reduce calcium conductances in invertebrate neurons. Voltage-activated calcium channels therefore appear to be an important target of ethanol action. However, the interactions of ethanol with specific types of calcium channels have yet to be defined. This study examined the effects of ethanol on two different populations of calcium channels in N1E-115 neuroblastoma and in NG108-15 neuroblastoma x glioma hybrid cells. Transient (type I) and long-lasting (type II) calcium channel currents were recorded with the whole-cell voltage clamp technique. At concentrations above 30 mM, ethanol reversibly suppressed both types of calcium channel currents, without changing the voltage dependence of activation. Concentration-response curves were essentially the same for type I and type II channels. Ethanol at concentrations of 100 and 300 mM blocked currents by approximately 15 and 40%, respectively. The voltage dependence of type I channel inactivation was not altered by ethanol concentrations as high as 300 mM, nor was there evidence of a use-dependent blocking action. The effects of ethanol on calcium channels were similar in NG108-15 cells; both channel types were blocked by ethanol at about the same concentrations as were effective in N1E-115 cells. Because ethanol interacts with opiate receptors in some systems, and leucine-enkephalin is known to block type II currents in NG108-15 cells, we examined whether the ethanol block of type II currents could be altered by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol effects on two types of voltage-activated calcium channels. 216 82

Individual G-proteins are highly similar in primary sequence. It is thus pertinent to ask what degree of specificity of interaction each of these display with the various receptors and effector systems. Many of the identified G-proteins are co-expressed in a single tissue or cell. As the extreme C-terminus of the alpha-subunit of each G-protein appears to be a key domain for the interactions of receptors and G-proteins, we have generated a series of G-protein-selective anti-peptide antisera against this region and then have used these antisera to attempt to interfere with receptor-G-protein coupling. With this approach, we have demonstrated that delta-opioid receptor-mediated inhibition of adenylate cyclase in neuroblastoma x glioma (NG108-15) cell membranes is transduced specifically by Gi2 and in the same cell that alpha 2-adrenergic inhibition of Ca2+ currents is transduced by G0.
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PMID:Specificity of interactions of receptors and effectors with GTP-binding proteins in native membranes. 217 90

The long-term modulation of calcium (Ca2+) currents (ICa) was studied in 108CC15 neuroblastoma x glioma hybrid (NxG) cells grown under various culture conditions. The following results were obtained: 1. Addition of 1 mM dibutyryl cyclic adenosine monophosphate (db-cAMP) or 0.1 microM forskolin to the culture medium increased a transient component of ICa two-fold within 3 days, from 21.0 +/- 1.6 pA/pF (n = 22) to a maximum of 40.0 +/- 2.6 pA/pF (n = 28). Under these conditions, cells also expressed a slowly inactivating ICa component (maximum after 3 days, 20.5 +/- 1.6 pA/pF, n = 28). 2. The fast inactivating ICa as well as the db-cAMP-induced slowly inactivating ICa were completely down-regulated during incubation of NxG cells with the inorganic Ca2+ channel blocker, nickel (Ni2+, 100 microM). The suppressing effect was reversed within 3 days of incubation in db-cAMP-containing medium lacking Ni2+. 3. Binding studies on membrane preparations of control and Ni2(+)-pretreated NxG cells revealed a marked difference in the maximal (+)3H-PN200-110 binding. The difference was seen in undifferentiated as well as in db-cAMP-incubated cells. 4. The protein synthesis blocker, cycloheximide, suppressed both the db-cAMP-induced increase and the reappearance of ICa following Ni2+ pretreatment. It is suggested that chronic application of db-cAMP or Ni2+ to NxG cells increases and decreases the number of Ca2+ channel proteins, respectively.
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PMID:Calcium currents of neuroblastoma x glioma hybrid cells after cultivation with dibutyryl cyclic AMP and nickel. 217 86

Endothelin-1, endothelin-3, and the snake venom toxin sarafotoxin S6b stimulate the hydrolysis of phosphatidylinositol by phospholipase C with similar potencies in primary cultures of astrocytes prepared from rat brain cortex. In indo 1-loaded cells, endothelin-1, endothelin-2, endothelin-3, and sarafotoxin induce the rapid mobilization of intracellular Ca2+ stores and promote a more slowly developing influx of Ca2+. These responses were insensitive to pertussis toxin and to inhibitors of cyclooxygenase and lipoxygenase. Similar actions of endothelins and sarafotoxin were observed using astrocytes from the cerebellum and glioma cells from the C6 and NN cell lines. The endothelin receptor of astrocytes differs from the receptor previously characterized in endothelial cells from brain microvessels in that it has a high affinity for endothelin-3. Thus, brain endothelin-1 and endothelin-3 have different target cells in the brain and may have different functions.
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PMID:Astrocytes are target cells for endothelins and sarafotoxin. 218 55

The effects of endothelin-1 (ET) on the signal transduction in rat and human glioma cell line cells have been investigated. ET was found to initiate the increase of intracellular calcium ([Ca2+]i) levels in both C6 and A-172 cells, which was concurrent with the formation of inositol 1,4,5-trisphosphate (IP3(1,4,5)). In the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) in the incubation media, the duration of the intracellular calcium response was reduced, indicating that the ET-induced increase of intracellular calcium in glioma cells may be mediated by a dual mechanism, intracellular calcium mobilization and influx of extracellular calcium. These results suggest that ET may also act as a neuropeptide in the central nervous system.
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PMID:Endothelin-1 induces intracellular calcium rise and inositol 1,4,5-trisphosphate formation in cultured rat and human glioma cells. 219 56

Two human glioma cell lines were examined for multidrug resistance (MDR). A vincristine (VCR)-resistant glioma cell line showed a cross resistance to Adriamycin (doxorubicin, ADR) and etoposide (VP-16) to varying extents, suggesting the presence of MDR; the resistance to VCR was considerably decreased by calcium entry blockers. On the other hand, another VCR-sensitive glioma cell line exhibited no cross resistance to ADR or VP-16. Double minute chromosomes and homogeneously staining regions as well as clonal aberrations of chromosome 7 were not observed in cytogenetic studies of multidrug-resistant and multidrug-sensitive glioma cell lines. In Northern and Southern blot analyses, MDR gene 1 (MDR1) messenger ribonucleic acid (mRNA) was shown to be overexpressed without any amplification of the MDR1 gene in multidrug-resistant glioma cell lines as compared to multidrug-sensitive glioma cell lines. It would be reasonable to suggest that amplification of the MDR1 gene may not be a sine qua non for acquisition of MDR and that the MDR1 mRNA level may be correlated with the extent of MDR.
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PMID:Amplification and expression of a multidrug resistance gene in human glioma cell lines. 229 93

Mechanisms for activation and for removal of cytosolic Ca2+ after stimulation with bradykinin were investigated in two neural cell lines by measuring cytosolic Ca2+ activity and 45Ca2+ fluxes. In the neuronal (neuroblastoma x glioma hybrid) and in the glial (rat glioma) cell lines, the transient, bradykinin-induced rise in cytosolic Ca2+ activity (determined by fura-2 or indo-1 fluorescence) was blocked by a bradykinin B2 receptor antagonist. Ca2+ ionophores (ionomycin and 4-Br-A23187) caused a comparable transient rise in cytosolic Ca2+ activity. After addition of ionophores, the Ca2+ response to bradykinin was reduced or completely blocked in both cell lines. At the concentrations used, the ionophores primarily depleted intracellular Ca2+ stores and prevented refilling of the stores. Thus, the bradykinin-induced rise of cytosolic Ca2+ activity seems to be mostly due to Ca2+ release from internal stores. In the neuronal but not in the glial cell line, a brief stimulation by bradykinin of 45Ca2+ uptake was followed by a long-lasting inhibition below control values. Thus, in the neuronal cells bradykinin presumably blocks Ca2+ channels by a readily reversible, pertussis toxin-insensitive mechanism. Excess cytosolic Ca2+ of the bradykinin-stimulated cells is mostly not resequestered into the internal Ca2+ pool accessible to bradykinin, but is mainly extruded through the plasma membrane, as indicated by (i) stimulation of 45Ca2+ release by bradykinin, (ii) quick reduction by bradykinin of cellular 45Ca2+ content of cells preequilibrated with 45Ca2+, and (iii) diminution of the ionophore-inducible Ca2+ response after the addition of bradykinin.
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PMID:Mechanisms for activation and subsequent removal of cytosolic Ca2+ in bradykinin-stimulated neuronal and glial cell lines. 229 36

Extracellular application of bradykinin and injection of inositol-1,4,5-trisphosphate (Ins-P3) induced a hyperpolarization in polyploid rat glioma cells. Ins-1,4,5-P3 and Ins-2,4,5-P3 were effective but not Ins-4,5-P2, Ins-1,3,4,5-P4 and Ins-1,3,4,5,6-P5. The reversal potential of the hyperpolarizing response induced by bradykinin or by Ins-P3 increased to a comparable degree with increasing the extracellular K+ concentration. Certain blockers of K+ channels, for example charybdotoxin (5-50 nM), Ba2+ (5-20 mM), 4-aminopyridine (5-10 mM) and quinidine (0.1-0.5 mM) reversibly suppressed the membrane potential response to bradykinin or to Ins-P3; however, apamin (1 microM) and D-tubocurarine (0.5 mM) had no effect. Intracellular injection of EGTA made the glioma cells unresponsive to bradykinin. Superfusion of the cells with Ca2(+)-free medium gradually and reversibly abolished the response to bradykinin, but only slightly reduced the effect of Ins-P3. The Ca2+ channel blockers Co2+ (1-5 mM), Mn2+ (2-6 mM) and nifedipine (1-20 microM), but not desmethoxyverapamil (100 microM) inhibited the hyperpolarizing effect of bradykinin. The hyperpolarization induced by Ins-P3, however, was not influenced by Mn2+ (1-5 mM) or by Co2+ (7 mM). Injection of Ca2+ into the glioma cells induced a hyperpolarization susceptible to Ba2+ and quinidine. Treatment of glioma cells with an activator or with inhibitors of protein kinase C or with pertussis toxin did not affect the response to bradykinin. Incubation of the cells with the Ca2+ ionophore A23187 (0.1-1 microM) made the cells unresponsive to bradykinin and, somewhat less, to Ins-P3. At these concentrations the Ca2+ ionophore primarily depletes intracellular Ca2+ stores. In summary, bradykinin, via B2-receptors (blocked by [Thi5,8, D-Phe7]-bradykinin) activates a K+ conductance in glioma cells following a rise of cytosolic Ca2+ activity most likely due to Ins-P3-mediated release of Ca2+ from internal stores. Entry of extracellular Ca2+ appears also to be involved in this process.
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PMID:Activation of a K+ conductance by bradykinin and by inositol-1,4,5-trisphosphate in rat glioma cells: involvement of intracellular and extracellular Ca2+. 230 62


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