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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dinoflagellate toxin maitotoxin (MTX) elicited a sustained increase of [Ca2+]i in C6 glioma cells. This response was inhibited by SK&F 96365, a blocker of receptor-mediated calcium entry. In C6 cells, endothelin-1 elicited a rapid but transient increase in [Ca2+]i, followed by a smaller sustained increase. SK&F 96365 inhibited the sustained increase in [Ca2+]i. In both C6 glioma cells and RIN insulinoma cells, MTX elicited a marked influx of 45Ca2+. SK&F 96365 inhibited MTX-induced 45Ca2+ influx by 95% at 30 microM. The L-type calcium channel blocker nifedipine, even at 10 microM, inhibited MTX-induced calcium uptake by only 20% in RIN cells and by only 10% in C6 cells. MTX elicited calcium-dependent phosphoinositide breakdown in both C6 and RIN cells. In both cell lines, the MTX-induced phosphoinositide breakdown was inhibited by 90% by SK&F 96365 at 30 microM. Endothelin-1 and carbamylcholine elicited phosphoinositide breakdown in C6 cells and RIN cells, respectively. The stimulations were unaffected by the presence of SK&F 96365 up to 100 microM. In RIN insulinoma cells, MTX elicited calcium-dependent release of insulin. SK&F 96365 at 30 microM inhibited MTX-induced insulin release by 75%, whereas nifedipine, even at 30 microM, inhibited release by only 10%. The blockade of MTX-induced responses by SK&F 96365 indicates that MTX increases intracellular calcium by interacting directly with a calcium-entry system that is similar, in its sensitivity to SK&F 96365, to the calcium-entry system activated by receptors that elicit phosphoinositide breakdown. Activation of phospholipase C and hormone release by MTX also are blocked by SK&F 96365 and, thus, may be secondary to the activation of such a calcium-entry system.
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PMID:Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry. 131 15

The linkage between the transmembrane signal transduction system utilized by endothelin and alterations in gene expression has been investigated in C6 glioma cells. Treatment of C6 cells with endothelin-1 caused a rapid and transient 5-fold increase in c-fos and c-jun mRNA levels, followed by a decrease at 4 h. Dose-response studies indicated that 1 nM endothelin-1 caused half-maximal induction of c-fos mRNA 0.5 h after treatment and that maximal induction was elicited with a concentration of 10 nM. Actinomycin D totally abolished the rapid increase in c-fos mRNA caused by endothelin, indicating that the effect is at the transcriptional level. Endothelin-1 caused a decrease in proenkephalin mRNA to 50% of control levels at 4 h after treatment and had no effect on histone H4 mRNA over a 24 h period that was examined. These data indicate that receptor binding of endothelin-1 leads to rapid changes in the expression of immediate-early response genes which may cause more prolonged changes in the expression of AP-1 and/or CREB target genes in the nervous system.
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PMID:Stimulation of c-fos and c-jun gene expression and down-regulation of proenkephalin gene expression in C6 glioma cells by endothelin-1. 133 50

Interactions between endothelin-1 (ET)-induced phosphoinositide (PI) hydrolysis and agents that increase Ca2+ influx (i.e. A23187 and ionomycin) or induce depolarization (i.e. KCl) were investigated using C6 glioma. A23187 dose-dependently potentiated ET (30 nM)- and ATP (100 microM)-induced [3H]inositol phosphate (IP) accumulation. This potentiation was associated with an increase in the maximal stimulation elicited by both ET and ATP but their EC50 values were unchanged. This effect of A23187 occurred at concentrations that did not affect basal PI turnover; i.e. 10 nM-3 microM. Ionomycin within the range of 1 nM-1 microM also significantly enhanced ET-induced PI breakdown and this effect was associated with an increase of [Ca2+]i. KCl in a concentration-dependent manner (14.7-54.7 mM) markedly inhibited PI breakdown elicited by ET and ATP, but had much less inhibition on basal activity and no effect on A23187- and ionomycin-induced responses. In parallel, KCl added before or after ET, sharply attenuated the increase of ET-induced [Ca2+]i but did not affect basal level or ionomycin-induced [Ca2+]i response. Neither the potentiation by A23187 nor the inhibition by KCl of ET-induced PI turnover was observed in cultured cerebellar astrocytes. Our results suggest that the cell type-specific regulation by Ca2+ ionophores and KCl on ET-induced PI metabolism is closely related to perturbation of [Ca2+]i.
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PMID:Potentiation by Ca2+ ionophores and inhibition by extracellular KCl of endothelin-induced phosphoinositide turnover in C6 glioma cells. 133

1. The vasoconstrictor peptide endothelin-1 caused a fast, transient rise in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in a neuronal cell line (mouse neuroblastoma x rat glioma hybrid cells 108CC15). The mechanism of activation of guanylate cyclase by endothelin-1 was investigated. The endothelin-1-induced rise depended on the release of internal Ca2+. 2. The stimulation of cyclic GMP synthesis induced by endothelin-1 was suppressed after preincubating the cells in medium containing haemoglobin (IC50 3 microM). Similarly, pretreatment of the cells with the L-arginine analogues, L-canavanine (IC50 60 microM) or NG-monomethyl-L-arginine (IC50 2.5 microM), inhibited the cyclic GMP response to endothelin-1. Therefore, endothelin-1 activates guanylate cyclase most probably via formation of nitric oxide, which is released from L-arginine. 3. The Ca2+ ionophore ionomycin induced a transient rise in cyclic GMP levels, which was also suppressed by preincubation in the presence of either haemoglobin or the L-arginine analogues L-canavanine or NG-monomethyl-L-arginine. Therefore, we conclude that ionomycin can activate guanylate cyclase by a mechanism involving nitric oxide formation, similar to that induced by endothelin-1. 4. The alkaloid veratridine, which activates Na+ channels and also causes influx of Ca2+ induced a transient rise of cyclic GMP levels in the neuronal cell line. This stimulation was blocked by pretreating the cells with L-canavanine, NG-monomethyl-L-arginine or haemoglobin. 5. Loading the cells with the Ca2+ chelator BAPTA suppresed the cyclic GMP response to application of endothelin-1, ionomycin, or veratridine. Thus, in the neuronal cell line a rise in cytosolic Ca2 + activity seems to be sufficient to stimulate the nitric oxide forming enzyme which synthesizes the activator of soluble guanylate cyclase.
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PMID:Endothelin and a Ca2+ ionophore raise cyclic GMP levels in a neuronal cell line via formation of nitric oxide. 196 7

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

The effects of Ca2+ on the translocation of conventional and new protein kinase C isozymes in intact cells were studied by using C6 glioma cells as a model system. Two conditions which monitor intracellular Ca2+ were performed: one is extracellular Ca(2+)-depletion by treating the cells with physiological saline solution (PSS) without Ca2+ but containing 0.5 mM EGTA, the other is treating the cells with 1 microM ionomycin to induce Ca(2+)-influx. In addition, the TPA and endothelin-1 induced translocations of conventional and new PKC isozymes under these two conditions were also comparatively studied. When the intact cells were treated with Ca(2+)-free, EGTA containing PSS, the membrane-bound conventional PKC alpha (cPKC alpha) was greatly reduced and cytosolic cPKC alpha was slightly increased. However, neither membrane bound nor cytosolic new PKC delta (nPKC delta) was affected by extracellular Ca(2+)-depletion. On the other hand, when the cells were treated with 1 microM ionomycin, the translocation of cPKC alpha itself was observed while nPKC delta was not affected. In extracellular Ca(2+)-depletion, the translocation of cPKC alpha induced by 100 nM TPA still occurred although the extent of translocation was smaller than that induced by TPA under normal Ca2+ conditions; however, that induced by 30 nM ET-1 was blocked. After the cells were treated with 1 microM ionomycin, the translocation of cPKC alpha induced by 30 nM TPA was further increased compared to 1 microM ionomycin or 30 nM TPA alone, while that induced by ET-1 was only slightly further increased. All these results suggested that in intact cells, the activation of cPKC alpha was operated by both the intracellular Ca2+ level and diacylglycerol and that of nPKC delta was operated by diacylglycerol alone as predicted by their properties from purified enzyme or cDNA. In addition, the translocation of cPKC alpha induced by the natural activator ET-1 seemed to be more dependent on Ca2+ than TPA in intact cells.
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PMID:Effects of Ca2+ on the activation of conventional and new PKC isozymes and on TPA and endothelin-1 induced translocations of these isozymes in intact cells. 802 77

In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) has been recognized to stimulate DNA synthesis in some cell lines. In this study, we confirmed the existence of ET-1 receptor in YKG-1 human glioma cells, and investigated its effect on DNA synthesis in YKG-1 for 6 consecutive days, comparing it with that of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Scatchard analysis of the binding data revealed the presence of a single class of high-affinity binding molecule. The apparent dissociation constant (Kd) was 5.2 x 10(-9) M and the maximal binding capacity (B max) was 4.7 x 10(4) sites/cell. The percentage of non-cycling cells was initially more than 85%, and decreased to 55.40%, 24.22%, 11.50%, and 7.51% on days 1, 2, 4, and 6, respectively, after ET-1 stimulation. Although ET-1 reduces the fraction of non-cycling cells more slowly than other growth factors such as EGF, PDGF and IGF-I, it reaches the same level as the others by day 6. These results indicate that YKG-1 human glioma cells have ET-1 receptors and that ET-1 initiates a peculiar slow induction of DNA synthesis in these cells, suggesting that secondary factors might exist to accelerate the DNA synthesis in response to ET-1.
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PMID:Effect of endothelin-1 as growth factor on a human glioma cell line; its characteristic promotion of DNA synthesis. 805 30

We have compared the characteristics of receptors for nucleotide analogues and the involvement of phospholipase C (PLC) in the effector mechanism in NG108-15 neuroblastoma and C6 glioma cells. The relative potency of these analogues to stimulate inositol phosphate (IP) formation is UTP > UDP >> 2-methylthio-ATP (2-MeSATP), GTP > ATP, CTP > ADP > UMP in NG108-15 cells and ATP > UTP > ADP > GTP > UDP >> 2Me-SATP, CTP, UMP, in C6 glioma cells. alpha, beta-Methylene-ATP, beta, gamma-methylene-ATP, AMP, and adenosine had little or no effect in both types of cells. The EC50 values were 3 and 106 microM for UTP in NG108-15 and C6 glioma cells, respectively. The EC50 value for ATP in C6 glioma cells was 43 microM. 2-MeSATP was threefold more potent than ATP in NG108-15 cells but had little effect in C6 glioma cells at 1 mM. In NCB-20 cells, a similar rank order of potency to that found in NG108-15 cells, i.e., UTP >> GTP > ATP > CTP, was observed. In both NG108-15 and C6 glioma cells, preincubation with ATP or UTP caused a pronounced cross-desensitization of subsequent nucleotide-stimulated IP production. ATP and UTP displayed no additivity in terms of IP formation at maximally effective concentrations. In contrast, endothelin-1, bradykinin, and NaF interacted in an additive manner with either nucleotide in stimulating PI hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heterogeneity of nucleotide receptors in NG108-15 neuroblastoma and C6 glioma cells for mediating phosphoinositide turnover. 829 16

Both the cytosol and membrane in C6 glioma cells express abundance of PKC alpha, delta, zeta and trace amount of PKC epsilon by Western blot analysis with isozyme-specific antibodies. These characteristics make this cell line a good model to study the properties of different classes of PKC isoforms in one cell type. Exposure of the cells to 100 nM TPA for 10 min resulted in the translocation of conventional PKC alpha (cPKC alpha) and new PKC delta (nPKC delta) and -epsilon from the cytosolic to the membrane fraction, while left atypical PKC zeta (aPKC zeta) unaffected. The extent of translocation of cPKC alpha induced by TPA was more prominent than that of nPKC delta and nPKC epsilon. alpha-TPA, the inactive phorbol ester, did not induce translocation of these isozymes. After treatment of the cells with 1 microM TPA for 17 h, cPKC alpha, nPKC delta and nPKC epsilon were almost completely down-regulated, whereas aPKC zeta was still unaffected. The natural activators of this cell line, endothelin-1 and ATP also translocated cPKC alpha and nPKC delta. However, the extent of translocation induced by these two agonists was much less than that of TPA.
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PMID:Protein kinase C alpha, delta, epsilon and zeta in C6 glioma cells. TPA induces translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC zeta. 840 36


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