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)

We studied the regulation of beta-adrenergic receptor (AR) subtypes co-existing in rat C6 glioma cells to clarify the importance of subtype ratio in responses to catecholamines. Radioligand binding studies with [125I]-cyanopindolol showed that beta 1- and beta 2-ARs co-existed in this cell line in approximately an 80:20 ratio. Norepinephrine (NE) and epinephrine (EPI) were equally potent in increasing cAMP accumulation, consistent with a primarily beta 1-response, although both beta 1- and beta 2-components of the response could be isolated using selective agonists (NE and zinterol), and antagonists (CGP 20712A and ICI 118,551). Little or no evidence of beta 3-ARs could be found in this cell line. Treatment of cells with 500 nM dexamethasone (DEX) for 48 hr increased the proportion of beta 2-ARs (20 to 60%). However, a reciprocal decrease in beta 1-ARs resulted in no change in total beta-ARs. Studies on the time-(12 to 72 hr) and concentration- (5 nM to 5000 nM) dependence of DEX treatment showed that increases in beta 2-ARs were closely linked to decreases in beta 1-ARs with little or no change in total receptor density observed at any time or in any concentration studied. Treatment with DEX also increased beta 2- and decreased beta 1-mediated cAMP responses, but did not alter the response to the nonselective agonist, isoproterenol. Northern blot analysis showed a 2- to 3-fold increase in beta 2-AR mRNA, but no change in beta 1-AR mRNA, after exposure to 50 or 500 nM DEX for 48 hr. Surprisingly, after DEX treatment, NE and EPI were still equally potent in activating cAMP accumulation, although responses to the beta 2-selective agonist, zinterol, were increased. These studies show a close reciprocal regulation by DEX of the relative proportions of beta 1- and beta 2-AR subtypes in C6 cells. The functional significance of the changing subtype ratios does not appear to be related to catecholamine responsiveness.
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PMID:Close reciprocal regulation of beta 1- and beta 2-adrenergic receptors by dexamethasone in C6 glioma cells: effects on catecholamine responsiveness. 790 14

Administration of carbachol, noradrenaline, and bradykinin induced Egr-1 mRNA expression within 1 h in mouse neuroblastoma x rat glioma hybrid NG108-15 cells. With specific receptor antagonists, the Egr-1 inductions by carbachol and noradrenaline were shown to be mediated via cholinergic muscarinic and alpha 2-adrenergic receptors, respectively. At their saturation levels for Egr-1 induction, the two agonists had additive effects when added together, but no prolongation of the effect on Egr-1 induction was observed. Addition of carbachol or noradrenaline 6 h after primary stimulation with carbachol or noradrenaline did not result in secondary Egr-1 induction, probably because of receptor desensitization. On the other hand, bradykinin consistently had an additive effect on Egr-1 induction, irrespective of the time of its addition, suggesting that the signal pathways for Egr-1 induction by carbachol or noradrenaline and by bradykinin are different. Treatment of cells with pertussis toxin or cholera toxin strongly inhibited Egr-1 induction by carbachol or noradrenaline but only partially inhibited the induction by bradykinin. Thus, the signals transduced in NG108-15 cells by different neurotransmitter receptors appear to have different effects on Egr-1 induction, depending on the times of stimulation and the combinations of receptors stimulated.
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PMID:Additive induction of Egr-1 (zif/268) mRNA expression in neuroblastoma x glioma hybrid NG108-15 cells via cholinergic muscarinic, alpha 2-adrenergic, and bradykinin receptors. 838 64

Transport of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) and (-)-norepinephrine was investigated in SarCNU-sensitive SK-MG-1 and -resistant SKI-1 human glioma cell lines. [3H]SarCNU influx was inhibited by SarCNU, sarcosinamide, and (+/-)-epinephrine in SK-MG-1 cells with competitive inhibition observed by (+/-)-epinephrine (Ki = 140 +/- 12 microM) and (+/-)-norepinephrine (Ki = 255 +/- 41 microM). No effect on influx was detected in SKI-1 cells. [3H](-)-Norepinephrine influx was linear to 15 sec in both cell lines and temperature dependent only in SK-MG-1 cells. Influx of [3H](-)-norepinephrine was found to be saturable in SK-MG-1 (K(m) = 148 +/- 28 microM, Vmax = 1.23 +/- 0.18 pmol/microL intracellular water/sec) but not in SKI-1 cells. In SK-MG-1 cells, [3H](-)-norepinephrine influx was found to be inhibited competitively by (-)-epinephrine (Ki = 111 +/- 7 microM) and SarCNU (Ki = 1.48 +/- 0.22 mM). Ouabain and KCl were able to inhibit the [3H](-)-norepinephrine influx in SK-MG-1 cells, consistent with influx being driven by membrane potential. Several catecholamine uptake2 inhibitors were able to reduce significantly the influx of [3H](-)-norepinephrine and [3H]SarCNU with no inhibition by a catecholamine uptake1 inhibitor. These findings suggest that increased sensitivity of SK-MG-1 to SarCNU is secondary to enhanced accumulation of SarCNU mediated via the catecholamine extraneuronal uptake2 transporter, which is not detectable in SKI-1 cells. The introduction of SarCNU into clinical trials will confirm if increased uptake via the catecholamine extraneuronal uptake2 transporter will result in increased antitumor activity.
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PMID:Characterization of the catecholamine extraneuronal uptake2 carrier in human glioma cell lines SK-MG-1 and SKI-1 in relation to (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) selective cytotoxicity. 868 79

Tritiated methylphenylpyridinium ([3H]MPP+), a substrate of the neuronal and extraneuronal noradrenaline transporter (uptake1 and uptake2, respectively) and of the organic cation transporter (OCT1), was used to characterize the amine transport system of the established human glioma cell line SK-MG-1. Uptake of [3H]MPP+ (25 nM) into SK-MG-1 cells increased linearly with time for up to 15 min. Selective uptake1 inhibitors (e.g. (+)oxaprotiline) or omission of Na+ or Cl-ions did not affect [3H]MPP+ uptake, whereas uptake2 inhibitors such as O-methyl-isoprenaline (OMI) or corticosterone as well as depolarizing concentrations of K+ or Ba2+ strongly reduced [3H]MPP+ uptake. Initial rates of OMI(100 microM)-sensitive [3H]MPP+ uptake were saturable, with a K(m) of about 17 microM and a maximal rate of about 50 pmol/(min x mg protein). IC50 (or Ki) values for inhibition of [3H]MPP+ uptake by substrates and inhibitors of uptake2 or OCT1 were highly significantly correlated with published IC50 values for inhibition of uptake2 but not with corresponding values for inhibition of OCT1. The results presented here clearly demonstrate that human glioma cells express an uptake2 transporter. Thus, glial cells in the human central nervous system endowed with this transporter are likely to contribute to the inactivation of neuronally released noradrenaline.
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PMID:Expression of the extraneuronal monoamine transporter (uptake2) in human glioma cells. 869 89

From studies on sympathetically innervated peripheral tissues it is well known that both neuronal and non-neuronal transport systems contribute to the inactivation of released monoamine transmitters. The close proximity between synapses and glia cell processes in the CNS leads to the so far unresolved question whether non-neuronal transporters are involved in the inactivation of centrally released monamine transmitters such as noradrenaline, dopamine and 5-hydroxytryptamine. 1-Methyl-4-phenylpyridinium (MPP+) is a prototypical substrate of the extraneuronal monoamine transporter (uptake2). [3H]MPP+ was found to accumulate in various human glioma cell lines. [3H]MPP+ transport was characterized in more detail in HTZ146 human glioma cells. The Ki values of various compounds for the inhibition of initial rates of [3H]MPP+ transport into HTZ146 cells were closely correlated with known Ki values for the inhibition of the extraneuronal monoamine transporter (P < 0.01, r = 0.991, n = 7). The rank order of inhibitory potencies was decynium 22 > corticosterone > cyanine 863 > O-methylisoprenaline > quinine > clonidine > quinidine. [3H]MPP+ accumulation was investigated not only in various CNS tumour cell lines but also in primary cultures of human astrocytes and rat cerebral cortex slices. In all tested experimental systems, accumulation was sensitive to cyanine-related inhibitors of the extraneuronal monamine transporter. These findings suggest that the extraneuronal monamine transporter exists in glia cells. Furthermore, it was shown that MPP+ is able to make use of the extraneuronal monoamine transporter not only to enter but also to leave glia cells. This finding suggests that the extraneuronal monoamine transporter may play a key role in the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.
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PMID:The extraneuronal transporter for monoamine transmitters exists in cells derived from human central nervous system glia. 875 96

Dopamine beta-hydroxylase catalyzes the final step in noradrenaline synthesis and is expressed exclusively in noradrenergic and adrenergic cells. In order to identify elements within the dopamine beta-hydroxylase (DBH) gene which contribute to the regulation of tissue-specific expression, we have analyzed the expression of the rat DBH promoter by transient transfection in both DBH-expressing and non-expressing cell lines. We have found that 1 kilobase of the DBH promoter can direct expression of the luciferase reporter gene in the DBH-expressing PC12, CATH.a, and SK-N-SH cell lines, but not in the non-DBH-expressing C6 glioma or CA77 cell lines. This activity was localized to a region between -133 and -173 upstream of the transcription start site. This element, however, also directed expression in non-DBH-expressing cell lines, but was inhibited when sequences between -212 and -388 were included. This inhibitory region contains sequences homologous to a silencer element recently identified in the human DBH gene, and shares homology with other previously identified silencer elements. Gel retardation experiments demonstrate that the rat DBH inhibitory region and the silencer elements found in the rat sodium type II channel and SCG10 genes bind a similar factor. The region between -133 and -173, which contains a consensus cyclic AMP response element (CRE), was also found to be responsive to cAMP in both DBH-expressing and non-expressing cells. Inclusion of sequences between -173 and -190 diminished the cAMP induction in PC12 cells, and nearly abolished the induction in C6 and CA77 cells, suggesting the presence of an additional negative element which inhibits cAMP induction in non-DBH expressing cells. DNA binding assays using antibodies to CRE binding protein-related transcription factors identified ATF-1 binding to the rat DBH-CRE, and further suggest that inhibition of cAMP regulation may be due to inhibition of ATF-1 binding by an additional factor, which binds to the DBH promoter immediately upstream of the CRE. These results demonstrate the importance of both positive and negative regulatory elements in the regulation of tissue-specific expression of the rat DBH gene.
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PMID:Positive and negative elements contribute to the cell-specific expression of the rat dopamine beta-hydroxylase gene. 901 68

The rat glioma cell line C6.9 has been recently reported to respond to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) by the induction of a programmed cell death. Since, in vivo, glial cells are thought to be exposed to several neurotransmitters, we investigated the possibility of a neurotransmitter-mediated inhibition of this active cell death process. Noradrenaline and the beta-adrenoceptor agonist isoproterenol showed significant inhibition of the 1,25(OH)2D3-induced programmed cell death. The beta-adrenoceptor antagonist propanolol reversed this inhibition, while the alpha-adrenoceptor antagonist yohimbin was devoid of any effect. This suggests that the efficiency of antiproliferative vitamin D-related therapies could be influenced by endogenous levels of noradrenaline.
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PMID:Noradrenaline inhibits the programmed cell death induced by 1,25-dihydroxyvitamin D3 in glioma. 904 12

1. Nitric oxide (NO) production in C6 glioma cells was directly monitored in real time by electrochemical detection with a NO-specific biosensor. 2. We present here the first direct evidence that noradrenaline elicits long-lasting NO production in C6 cells pretreated with lipopolysaccharide and interferon-gamma, an effect blocked by NG-monomethyl-L-arginine, a NO synthase inhibitor. 3. This direct electrochemical measurement of glia-derived NO should facilitate our understanding of the kinetics of glial signaling in glia-glia and glia-neuron networks in the brain.
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PMID:Direct and continuous electrochemical measurement of noradrenaline-induced nitric oxide production in C6 glioma cells. 961 1

Glial cells have a role in maintaining the function of neural cells. This study was undertaken to clarify the effects of baicalin and baicalein, flavonoids isolated from an important medicinal plant Scutellariae Radix (the root of Scutellaria baicalensis Georgi), on glial cell function using C6 rat glioma cells. Baicalin and baicalein caused concentration-dependent inhibition of a histamine-induced increase in intracellular Ca2+ concentrations ([Ca2+]i). The potency of baicalein was significantly greater than that of baicalin. The noradrenaline- and carbachol-induced increase in [Ca2+]i was also inhibited by baicalein and both drugs inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+]i. These results suggest that baicalin and baicalein inhibit [Ca2+]i elevation by reducing phospholipase C activity. The inhibitory effects of baicalin and baicalein on [Ca2+]i elevation might be important in the interpretation of their pharmacological action on glial cells, such as inhibition of Ca2(+)-required enzyme phospholipase A2.
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PMID:Baicalin and baicalein, constituents of an important medicinal plant, inhibit intracellular Ca2+ elevation by reducing phospholipase C activity in C6 rat glioma cells. 982 67

The ability of cloned human alpha2B-adrenoceptors heterologously expressed in Sf9 cells and endogenous alpha2B-adrenoceptors in NG 108-15 neuroblastoma x glioma cells to couple to increase of intracellular Ca2+ was studied. Ca2+ increases in NG 108-15 cells were detectable but slight, whereas those in alpha2B-adrenoceptor-expressing Sf9 cells were greater. In the latter, the maximum Ca2+ increase correlated positively, and the EC50-value of noradrenaline negatively, with the receptor expression density. The order of potency of the agonists was D-medetomidine ([D]-4-[5]-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) > noradrenaline approximately = clonidine > oxymetazoline, with clonidine and UK14,304 (5-bromo-N-[4,5-dihydro-1H-imidazole-2-yl]-6-quinoxalinamine) being weak partial agonists. In Sf9 cells Ca2+ increases consisted of concomitant mobilization from an intracellular store and influx of extracellular Ca2+. In these cells alpha2B-adrenoceptor stimulation also increased the inositol 1,4,5-trisphosphate mass. We conclude that alpha2B-adrenoceptors can couple to intracellular Ca2+ increases which may involve prior activation of phospholipase C.
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PMID:Alpha2B-adrenoceptors couple to Ca2+ increase in both endogenous and recombinant expression systems. 987 83


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