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)

1. Pharmacological and kinetic properties of high-voltage-activated (HVA) Ca2+ channel currents were studied using the whole-cell and perforated patch-clamp methods in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, differentiated by dibutyryl cyclic AMP or by prostaglandin E1 and theophylline. 2. The HVA currents were separated into two components by use of two organic Ca2+ channel antagonists, omega-conotoxin GVIA (omega CgTX) and a dihydropyridine (DHP) compound, nifedipine. One current component, IDHP, was blocked by nifedipine (Kd = 8.2 nM) and was resistant to omega CgTX. Conversely, the other component, I omega CgTX, was irreversibly blocked by omega CgTX and was resistant to DHPs. Thus, IDHP could be studied in isolation by a short application of omega CgTX, while I omega CgTX could be studied in the presence of nifedipine. 3. The voltage for half-activation of IDHP was smaller than that of I omega CgTX by 13 mV. IDHP was activated at potentials that were subthreshold for voltage-dependent K+ currents of the cell, whereas I omega CgTX was not. 4. Time courses of activation and deactivation of IDHP were faster than those of I omega CgTX. 5. Voltage-dependent inactivation was small for both IDHP and I omega CgTX at any potential. 6. Ca(2+)-dependent inactivation of IDHP was faster and more prominent than that of I omega CgTX. The time course of the Ca(2+)-dependent inactivation of IDHP, but not I omega CgTX, was slowed as the membrane potential was made more positive between -20 and 30 mV, although amplitude of the current was increased. 7. Alkaline earth metal ions carried the two components of IHVA in the same order: Ba2+ greater than Sr2+ greater than Ca2+. 8. Metal ions blocked the two components of IHVA in the same order of potency: Gd3+ greater than La3+ greater than Cd2+ greater than Cu2+ greater than Mn2+ greater than Ni2+. 9. An alkylating agent, N-ethylmaleimide (NEM, 0.1 mM), selectively augmented IDHP by 30%. 10. During the course of cellular differentiation induced by dibutyryl cyclic AMP, IDHP appeared earlier than I omega CgTX. 11. These results indicate that two classes of Ca2+ channels contribute to the HVA currents of this cell line. The DHP-sensitive channel is more apt to generate Ca2+ spikes and Ca2+ plateau potentials than the omega CgTX-sensitive channel.
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PMID:Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line. 137 34

Neuroblastoma x glioma hybrid NG108-15 cells express a high-affinity IP prostanoid receptor. Saturation binding analysis of this receptor, using [3H]prostaglandin E1 ([3H]PGE1) as ligand, indicated that it was present at some 1.5 pmol/mg of membrane protein and displayed a dissociation constant for this ligand of 30-40 nM. Prolonged exposure of these cells either to PGE1 or to iloprost, which is a stable analogue of prostacyclin, caused a 40-70% decrease in levels of the receptor. The remaining receptors were capable of interacting with the stimulatory G-protein (Gs) of the adenylate cyclase cascade, as saturation analysis of the binding of [3H]PGE1 indicated that they had a similar affinity for the 3H-labelled ligand, and because the specific binding of [3H]PGE1 to these receptors was still sensitive to the presence of poorly hydrolysed analogues of GTP. We have recently demonstrated that prolonged exposure of NG108-15 ells to PGE1 causes a cyclic AMP-independent loss of Gs alpha-subunit (Gs alpha) from these cells [McKenzie & Milligan (1990) J. Biol. Chem. 265, 17084-17093]. Steady-state concentration of the larger 45 kDa form of Gs alpha (which is the predominant form expressed in these cells) was assessed to be 9.6 pmol/mg of membrane protein, and treatment with iloprost decreased levels of this polypeptide to some 3.0 pmol/mg of protein. Time courses of iloprost-mediated down-regulation of the IP prostanoid receptor, loss of Gs alpha protein as assessed by immunoblotting and loss of Gs alpha activity as assessed by the reconstitution of NaF stimulation of adenylate cyclase activity to membranes of S49 cyc- cells by sodium cholate extracts of NG108-15 cells were identical, suggesting that the loss of the IP prostanoid receptor and G-protein occurred in parallel. Each of these effects was half-maximal between 2 and 3 h of exposure to the agonist. Stoichiometry of loss of Gs alpha and IP prostanoid receptor was unchanged by the percentage receptor occupancy, and quantification indicated the loss of some 7-10 mol of Gs alpha/mol of receptor. This is the first report to demonstrate the temporal concurrence of loss of Gs alpha and of a receptor which interacts with this G-protein. Chronic activation of the IP prostanoid receptor on these cells results in the development of a heterologous form of desensitization to agents which function to activate adenylate cyclase [Kelly, Keen, Nobbs & MacDermot (1990) Br. J. Pharmacol. 99, 306-316]. Agonist regulation of Gs alpha levels in these cells may contribute to this process.
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PMID:Concurrent down-regulation of IP prostanoid receptors and the alpha-subunit of the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure of neuroblastoma x glioma cells to prostanoid agonists. Quantification and functional implications. 137 45

Exposure of C62B rat glioma cells to fresh medium containing fetal bovine serum induced a sensitization of the subsequent ability of isoproterenol and forskolin to stimulate cyclic AMP accumulation, compared to cells exposed to fresh medium without serum. Isoproterenol stimulation was typically increased by 2- to 4-fold and forskolin stimulation by 3- to 5-fold. Sensitization occurred rapidly, was rapidly reversible and appeared to result from an increase in maximal stimulation. A commercial preparation of albumin, purified chromatographically so as to retain bound lipids and other factors, was able to mimic the effect of serum. In contrast to the effects of serum, exposure of cells to phorbol 12-myristate, 13-acetate induced little or no change in forskolin stimulation but a marked desensitization of isoproterenol stimulation that was due primarily to a decrease in potency. Neither the protein kinase C inhibitor staurosporine or overnight exposure to phorbol 12-myristate, 13-acetate to down-regulate protein kinase C prevented serum-induced sensitization. Pertussis toxin almost completely blocked serum-induced sensitization, suggesting involvement of a pertussis toxin-sensitive guanine nucleotide-binding protein in mediating the effects of serum. Sensitization was poorly retained in membrane adenylate cyclase assays. Studies with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, direct assays of cyclic AMP degradation by intact cells and assays of phosphodiesterase activity in cell lysates all indicated that degradation of cyclic AMP was decreased in serum-pretreated cells. Thus, both increased cyclic AMP synthesis and decreased cyclic AMP degradation may contribute to sensitization in these cells.
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PMID:Serum-induced sensitization of cyclic AMP accumulation in C62B rat glioma cells. 138 77

Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced. Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1 receptor gene is organized into two exons separated by a small intron in the 5' untranslated region of its mRNA. The transcription start site is located 864 bp upstream from the translational initiation site. The 5'-flanking sequences of the D1 receptor gene do not contain TATA and CAAT canonical sequences, but have a high G+C content, potential cyclic AMP and glucocorticoid response element sequences, and binding sites for transcription factors such as Sp1, Ap1, and Ap2. Transfection studies using the D1 5'-flanking sequence and CAT gene fusion constructs have demonstrated that (1) the D1 promoter is active in D1-expressing neuroblastoma NS20Y cells, but inactive in D1-deficient glioma C6 and kidney 293 cells, (2) the information contained within 735 bp of 5'-flanking sequence of the D1 gene appears to be sufficient to confer its cell-specific expression, and (3) the D1 gene promoter responds to cyclic AMP induction, suggesting the existence of an auto-regulation mechanism by which the stimulation of D1 receptor exerts a positive feedback on its own gene expression.
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PMID:Characterization of gene organization and promoter region of the rat dopamine D1 receptor gene. 140 30

8-Chloroadenosine 3':5'-monophosphate (8ClcAMP) inhibits the growth of human glioma cell lines at much lower concentrations than more commonly used cyclic AMP analogues, without inducing morphological differentiation. The mechanism by which 8ClcAMP exerts this effect is not fully understood. We examined whether the growth-inhibitory effect of this compound is due to an active metabolite, using a sulforhodamine protein stain assay to determine the proliferation rate of the WF human glioma cell line. 8-Chloroadenosine, one of the metabolites, inhibited the proliferation of WF human glioma cells more potently than 8ClcAMP. In the presence of adenosine deaminase, which converts 8-chloroadenosine into 8-chloroinosine, 8-chloroadenosine no longer inhibited human glioma cell growth. Addition of adenosine deaminase also largely reduced the growth-inhibitory effect of 8ClcAMP, but not of 8-(4-chlorophenylthio)cAMP. High performance liquid chromatography analysis revealed that at least part of the 8ClcAMP in the culture medium is converted into 8-chloroadenosine. We concluded that 8ClcAMP exerts its growth-inhibitory effect through its active metabolite 8-chloroadenosine. Adenylate cyclase assays showed that 8-chloroadenosine does not affect the intracellular cAMP production through adenosine A1 or A2 receptor activation, which makes it unlikely that 8-chloroadenosine inhibits glioma cell growth by increasing the intracellular cyclic AMP concentration.
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PMID:Growth inhibition of human glioma cells induced by 8-chloroadenosine, an active metabolite of 8-chloro cyclic adenosine 3':5'-monophosphate. 161 76

Incubation of rat glioma C6 cells with 10 microM desipramine for five days in vitro resulted in a 31% reduction of beta-adrenoceptors and a 38% reduction in isoproterenol-stimulated cyclic AMP accumulation. In contrast, forskolin or cholera toxin-stimulated cyclic AMP was unaffected by desipramine. Surprisingly, the beta-adrenoceptor desensitization was accompanied by an increase in the ratio of dissociation constants (KL/KH) for the low and high affinity states of the beta-adrenoceptor respectively and supports the concept of a complex interaction between the receptor and Gs protein.
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PMID:Chronic exposure of C6 glioma cells to desipramine desensitizes beta-adrenoceptors, but increases KL/KH ratio. 164 2

Mouse neuroblastoma x rat glioma hybrid cells (N x G, 108CC15) were used to study the inhibitory effects of the synthetic opioid D-Ala2-D-Leu5-enkephalin (DADLE), somatostatin, adrenaline-alpha 2 and angiotensin II on voltage-dependent Ca(2+)-currents (ICa) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N x G cells with pertussis toxin or intracellular infusion of GDP beta S indicating an involvement of a pertussis toxin sensitive GTP-binding protein (G-protein), presumably Go. The effect of DADLE, the strongest inhibitor of ICa, was studied during dibutyryl cyclic AMP (dBcAMP) induced differentiation. Using omega-conotoxin GVIA (omega-CTX) and methoxyverapamil (D600) as specific Ca(2+)-channel blockers of the N- and L-type Ca(2+)-channels, it was found that in N x G cells DADLE predominantly induces inhibition of T- and N-type Ca(2+)-channels.
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PMID:Inhibitory modulation of fast and slow Ca(2+)-currents in neuroblastoma x glioma cells during differentiation. 165 35

C6 glioma cells in culture were treated with 1 mM dibutyryl cyclic AMP (Db-cAMP) for 5, 8, 24 and 72 h. The cells were labelled with [3H]-thymidine before either the end, or the beginning, of the Db-cAMP treatment. The cell cycle passage was monitored by the simultaneous determination of DNA content and DNA synthesis in propidium iodide stained autoradiograms. The data revealed an early (t less than or equal to 3-8 h) and moderate inhibitory effect of Db-cAMP on all phases of the cell cycle except mitosis; some cells (2%) were completely blocked in the S phase. Later (8 less than t less than 24-72 h), the cycling of a substantial part of the population became inhibited in G1 phase. Microdensitometric texture analysis of Feulgen-stained nuclei, performed 24 h after administration of Db-cAMP, showed a higher inhomogeneity of the DNA distribution in cell nuclei, caused by the condensation of a part of the chromatin. This may reflect either changes in genome expression taking part in the process of cAMP induced differentiation or transit of some cells into quiescent G0 or S0 phases.
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PMID:Changes in cell cycle and chromatin distribution in C6 glioma cells treated by dibutyryl cyclic AMP. 166 44

The 2- and 6-fluoro derivatives of the potent beta-adrenergic agonist 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol were prepared and their adrenergic properties examined. The order of potency was as follows: beta-adrenergic activity (simulation of cyclic AMP formation in C6 glioma cells), 2-F = parent much greater than 6-F; beta 1-activity (rate of contraction, guinea pig atria), parent greater than 2-F much greater than 6-F; beta 2-activity (relaxation of guinea pig tracheal strip), 2-F greater than parent much greater than 6-F. The affinity of the 2-fluoro analogue for beta 1-adrenergic receptors (inhibition of the specific binding of [3H]dihydroalprenolol, rat cerebral cortical membranes) was 2 times greater, while the 6-fluoro analogue was 1450 times less than the parent. These results suggest that the aromatic rings of phenoxypropanolamine adrenergic agonists and phenylethanolamine adrenergic agonists bind in similar fashion to the adrenergic receptor, and that if interactions between fluorine and the side-chain hydroxyl group are critical in defining beta-adrenergic selectivity, the interactions are similar in both phenoxypropanolamines and phenylethanolamines.
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PMID:Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol. 167 55

Previous studies from this laboratory have shown that C-6 rat glioma cells (2B clone) exhibit specific phenotypic characteristics depending on passage in culture and that these populations respond differentially to addition of various exogenous compounds to the medium. Early passage (less than 25) C-6 glial cells express low glutamine synthetase activity (a marker for astrocytes) and with increasing cell passage (greater than 70) C-6 glial cells express more astrocytic properties with respect to both glutamine synthetase (GS) and morphology. In this study, cells from both early (glioblastic) and late (astrocytic) passage were examined for their response to the phospholipid, platelet-activating factor (PAF). We found that PAF increased GS activity in early passage (glioblastic) cells and more importantly it increased GS activity in late passage cells, already committed to the astrocytic phenotype. Furthermore, cells from both passages failed to respond to addition of lyso-PAF, the non-biologically active analog of PAF, to the medium. By following the uptake of 3H-PAF into cells, we observed that greater than 90% of the phospholipid was taken into the cells within the first hour of incubation. We compared the PAF effects with that of dibutyryl cyclic AMP (dBcAMP) and RO20-1724, a phosphodiesterase inhibitor. Cells from the early passage responded to both dBcAMP and RO20-1724 treatments with a significant increase in GS activity whereas cells from the late passage showed no significant change, confirming earlier reports from this laboratory. These findings indicate that the response of C-6 glioma cells to PAF (at least in the late passage) is not mediated via cyclic AMP. We suggest that in early passage cells PAF promotes expression of the astrocytic phenotype and in late passage cells PAF mediates a gliosis-type response.
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PMID:Platelet-activating factor increases glutamine synthetase activity in early and late passage C-6 glioma cells. 167 34


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