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

Voltage-sensitive calcium channels ( VSCCs ) have been identified in three clonal cells. These are the neuroblastoma X Chinese hamster brain hybrid ( NCB -20), the neuroblastoma X glioma hybrid (NG108-15), and the neuroblastoma ( N4TG1 ). Depolarization of NCB -20 cells with 50 mM KCl or 50 microM veratridine (VE) produced a 2- to 3-fold increase in net 45Ca2+ uptake. In NCB -20 cells, this voltage-sensitive 45Ca2+ uptake was inhibited selectively by organic calcium antagonists such as nitrendipine, cinnarizine, verapamil, and diltiazem (IC50 values = 6.4, 750, 1800, and 4500 nM, respectively). High K+-induced uptake was unaffected by 4-aminopyridine, tetraethylammonium, and tetrodotoxin (TTX), whereas VE-induced 45Ca2+ uptake was completely blocked by 3 microM TTX. In contrast to NCB -20 cells, NG108-15 cells showed a much smaller response to depolarizing stimuli. Following differentiation of NG108-15 cells by chronic treatment with 10 microM prostaglandin E1 and 50 microM 3-isobutyl-1-methylxanthine, depolarization induced a large increase in voltage-sensitive 45Ca2+ uptake. This induction was apparent after 24 hr and increased linearly for 96 hr. VSCC activity was also induced by 1.5% dimethyl sulfoxide and by other agents that increase intracellular cAMP, such as forskolin (1 microM) and cholera toxin (1 microgram/ml). Voltage-sensitive 45Ca2+ uptake in differentiated NG108-15 cells was inhibited by nitrendipine, D-600, and diltiazem (IC50 values = 7, 690, and 1600 nM). Our results suggest that VSCCs in neuronal clonal cell lines can be altered by cellular differentiation. In contrast to those VSCCs involved in neurotransmitter release, the VSCCs described here appear to be blocked by organic calcium channel antagonists at very low concentrations.
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PMID:Identification and characterization of voltage-sensitive calcium channels in neuronal clonal cell lines. 620 53

The kinetic parameters that determine the accumulation of cAMP in WI-38 cells stimulated with prostaglandin E1 have been determined at 37 degrees C and at lower temperatures. For desensitized cells, a reduction of temperatures from 37 degrees to 25 degrees C reduced both rate of synthesis and rate of elimination of cAMP by about 40%. The steady-state accumulation was, therefore, about the same at both temperatures. The extent of desensitization was also shown to be comparable at the two temperatures. It can be inferred that there was appreciable desensitization at 4 degrees C after a period of stimulation of less than one hour. This is contrasted with the behavior of C6-2B glioma cells at the same temperature. Escape of cAMP through the plasma membrane showed a greater temperature dependence than any of the other processes concerned with cAMP accumulation.
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PMID:Temperature effects on cyclic AMP accumulation in cultured fibroblasts. 624 72

Potentiation of the morphine inhibition of adenylate cyclase activity in the neuroblastoma N18TG2 cell line after sulfatide incorporation has been observed previously and a similar sulfatide effect on enkephalin inhibition was investigated. Conditions for the sulfatide incorporation were defined. Though N18TG2 cells possess a high affinity for 3H-D-Ala2-Met5 enkephalinamide (14 nM), the met5-enkephalin was relatively inactive in inhibiting the intracellular cAMP level. The IC50 value for met5-enkephalin to inhibit the prostaglandin E1 (PGE1) stimulated cAMP product was 65 nM in N18TG2 as compared to the IC50 value of 3 nM in the neuroblastoma x glioma NG108-15 hybrid. Upon exposure of the N18TG2 cells to 22 microM of sulfatide in the growth medium for 6 hours, both the potency and efficacy of the met5-enkephalin in sulfatide treated cells were found to be 3.4 nM. The degree of potentiation was dependent on the quantity of CS added to the growth medium and the age of the culture. Furthermore, the sulfatide effect appeared to be at the adenylate cyclase complex. Basal and PGE1-stimulated adenylate cyclase activity in the cellular membrane was similarly affected by enkephalin after sulfatide incorporation. There was a lipid specificity, since in the group of lipids tested only CS and PC exhibited the potentiation effect.
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PMID:Enkephalin inhibition of adenylate cyclase activity in neuroblastoma N18TG2 cells: effect of sulfatide incorporation. 624 77

C6 glioma cells grown in medium containing fetal bovine serum have a decreased beta-adrenergic receptor number and beta-receptor-stimulated cyclic AMP accumulation as compared to cells grown in a serum-free, defined medium. The decreased number of receptors and decreased cAMP accumulation are attributable to a suppression of receptor binding and response by serum as opposed to increases produced by growth in the defined medium. Serum, when added to cells grown in the absence of serum, stimulated cellular cyclic AMP levels to 2-3 times basal levels. This direct stimulatory effect was blocked by incubation of the cells with the beta-adrenergic antagonist propranolol and was partially reversed by dialysis of the serum. In contrast, addition of serum to cells that have been grown with serum fails to stimulate cyclic AMP accumulation. The decrease in receptors following growth in serum can be mimicked by growing cells in serum-free medium in the presence of beta-adrenergic agonists such as isoproterenol or norepinephrine. Radioenzymatic assays indicate that fetal bovine serum contains approximately 0.3 nM norepinephrine and lower concentrations of epinephrine. It thus appears that growth of C6 cells in serum-containing media desensitizes the beta-adrenergic receptor/cyclic AMP system of these cells. This desensitized state appears to result primarily from the action of catecholamines present in serum. These data indicate that retained catecholamines are one component in serum that can modify expression of beta-adrenergic receptors and hormonal response of cultured glioma cells.
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PMID:Serum catecholamines desensitize beta-adrenergic receptors of cultured C6 glioma cells. 626 45

We have cloned DNA complementary to mRNA coding for rat C6 glioma cell lactate dehydrogenase M-subunit. Double-stranded DNA complementary to a portion of lactate dehydrogenase mRNA was inserted into the Pst I site of plasmid pBR322 by the dC.dG tailing technique and amplified in Escherichia coli HB101. A recombinant plasmid containing lactate dehydrogenase cDNA was identified by colony hybridization to a cDNA prepared from partially purified lactate dehydrogenase mRNA and by hybridization-selected translation. The recombinant plasmid (pRLD42) contains a 680 nucleotide insert of lactate dehydrogenase mRNA. Hybridization of nick-translation pRLD42 to glioma cell poly(A)+RNA separated on agarose gel and transferred to nitrocellulose exhibited Mr = 5.9 X 10(5) for lactate dehydrogenase mRNA. Furthermore, Northern blot analysis of RNA from unstimulated and isoproterenol-stimulated glioma cells indicated a 2-fold increase of lactate dehydrogenase mRNA molecules in stimulated cells. The 2-fold increase of lactate dehydrogenase mRNA was confirmed by RNA-excess kinetic hybridization using pRLD42 DNA and poly(A)+RNA from unstimulated, isoproterenol-, and dibutyryl cAMP-stimulated glioma cells. These data demonstrate that isoproterenol and dibutyryl cAMP cause an increase of the number of lactate dehydrogenase M-subunit mRNA molecules in glioma cells which, in part, determines the extent of synthesis of the lactate dehydrogenase M-subunit.
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PMID:Cyclic AMP regulation of lactate dehydrogenase. Quantitation of lactate dehydrogenase M-subunit messenger RNA in isoproterenol-and N6,O2'-dibutyryl cyclic AMP-stimulated rat C6 glioma cells by hybridization analysis using a cloned cDNA probe. 627 88

The cAMP content of intact cells as well as adenylate cyclase of the membrane-rich particulate fractions was studied with C6 glioma cells that had been exposed to the culture medium supplemented with islet-activating protein (IAP), one of the pertussis toxins. Both the increase in the cellular cAMP content in response to a beta-adrenergic agonist and the stimulation of membrane adenylate cyclase by the beta-agonist and/or GTP were markedly enhanced by the IAP treatment of C6 cells, but no change was induced in affinities of the agonist (or an antagonist) or GTP for their respective sites of action (or binding). The concentration of IAP required for the half-maximal enhancement was as low as 1 pg/ml, when the time of cell exposure to the toxin was prolonged to 18 h. No enhancement was observed for the basal cAMP content or basal enzyme activity, nor was activation of adenylate cyclase by Gpp(NH)p (or NaF) affected by IAP treatment. The Vmax value of a specific and low Km GTPase was significantly smaller in the membranes of IAP-treated cells than in those of control cells. Cholera toxin treatment of cells activated adenylate cyclase without exerting any influence on these IAP actions. Thus, IAP would appear to enhance beta-receptor-coupled stimulation of adenylate cyclase, in a manner distinct from cholera toxin, by rendering more GTP available to the GTP sites on the regulatory subunit of the receptor-enzyme system.
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PMID:Modulation by islet-activating protein of adenylate cyclase activity in C6 glioma cells. 627 48

A doubly transformed rat glioma cell line, designated C6V-1, was obtained from rat glioma C6 cells by infection with a rat-adapted variant of Moloney sarcoma virus (MSV-M-os). The C6V-1 cells show karyotypic changes in chromosome number (43) and structure, while C6 cells possess a normal male karyotype. C6V-1 and C6 cells were employed for characterization of a receptor-adenylate cyclase system of the surface membrane. C6V-1 cells showed lower adenylate cyclase activity than that of C6 cells, though the apparent Km for ATP in both types of cells was the same. The maximal stimulation of adenylate cyclase by isoproterenol was significantly reduced, and Kact for isoproterenol was approximately 18-fold lower in C6V-1 cells. When the concentration of beta-adrenergic receptors was measured by various concentrations of [3H] dihydroalprenolol (DHA), the maximal binding sites of C6 and C6V-1 cells were 760 and 230 fmol/mg protein, respectively, without any changes in the association constant for DHA. The concentration of isoproterenol required for 50% displacement of the [3H] DHA binding (Kd) was the same (around 1.5 X 10(-6)M) in both cells, measured in the presence of GTP. Thus the 19-fold drop in the Kd/Kact ratio in C6V-1 cells suggests an incomplete coupling of beta-receptors to adenylate cyclase. Cyclic AMP phosphodiesterase activity and cAMP content in C6V-1 were lower than in C6 cells. Mitochondrial monoamine oxidase and cytosomal enolase activities, however, were somewhat higher in C6V-1 cells. The results indicate that a set of changes in the receptors and in the cyclic AMP system of C6V-1 is one of the specific alterations by transformation, even though those may not be the cause of cell transformation.
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PMID:Receptor-associated changes of the catecholamine-sensitive adenylate cyclase in glioma cells doubly transformed with Moloney sarcoma virus. 627 81

The paramyxoviruses measles (subacute sclerosing panencephalitis, SSPE) virus and canine distemper virus (CDV) cause an impairment of the catecholamine-induced beta-adrenergic receptor-dependent cAMP generation in persistently infected C6 rat glioma cells. In C6 cells persistently infected with CDV the number of receptors is greatly reduced. Hirata and Axelrod have shown that the number of beta-adrenergic receptors could be regulated by methylation of phosphatidylethanolamine, resulting in lecithin synthesis [Hirata, F. & Axelrod, J. (1980) Science 209, 1082-1090]. We have therefore studied the methylation of phosphatidylethanolamine in persistently infected cells by the incorporation of [3H]methyl groups from [methyl-3H]methionine into phosphatidylethanolamine. In both infected systems, C6/ SSPE and C6/CDV, we observed a total loss of catecholamine-stimulated beta-adrenergic receptor-dependent methylation, whereas the beta-receptor-independent methylation of phospholipids was unchanged.
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PMID:Alteration in phospholipid methylation and impairment of signal transmission in persistently paramyxovirus-infected C6 rat glioma cells. 628 59

Increased cellular adhesion has been postulated to be an early event required of neuroblasts undergoing neurite extension during differentiation. Nerve growth factor (NGF) induces neurite extension in a variety of cell types of neural crest origin. In the PC12 rat pheochromocytoma cell line, which has been proposed as a model for precursor cells to sympathetic neurons, NGF and dibutyryl cyclic AMP (dBcAMP) promote both neurite extension and an increased rate of cell-substrate adhesion. Since dBcAMP can substitute for NGF in this enhancement of adhesion rate in the PC12 cell line, cAMP has been suggested as a second messenger for NGF. We have shown that in two nearly diploid adrenergic like human neuroblastoma clones, the KA and SY5Y cell lines, which also extend neurites in response to both NGF and dBcAMP, only NGF enhances cellular adhesion, as defined by an increase in the number of cells cells prelabeled with 35S-methionine which attach to culture dishes at a given time. Incubation with monospecific antibodies directed against murine beta-NGF abolishes the NGF effect on adhesion. The NGF effect on human neuroblastoma is specific insofar as NGF does not facilitate adhesion of two glioma lines. Unlike the results obtained for PC12, in both SY5Y and KA lines, 1 mM dBcAMP decreases the rate of adhesion to levels significantly below those of controls. Adhesiveness of neuroblastoma cells treated with both NGF and dBcAMP is intermediate between that of cells treated with either agent alone. While theophylline mimics the dBcAMP effect, sodium butyrate has no such effect. At 22 degrees C, the effect of NGF on neuroblastoma substrate adhesion is observable within 5 minutes and persists for 2 hours; treatment of the KA line with NGF at 37 degrees C for 24 hours results in a more persistent enhancement of cell adhesion. Furthermore, both SY5Y and KA exhibit different morphologies when challenged with NGF, dBcAMP, or sodium butyrate. This study suggests that NGF and cyclic AMP do not share a common mechanism of action, but can in fact interact antagonistically in an adrenergic like neuroblastoma model system. Furthermore, the results suggest that increased cellular adhesiveness may not be an obligatory prerequisite for neurite extension by neuroblasts in development.
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PMID:Nerve growth factor and cyclic AMP: opposite effects on neuroblastoma-substrate adhesion. 629 16

The mechanism of isoproterenol and N6,O2-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) induction of lactate dehydrogenase A subunit mRNA (mRNALDH) was investigated in the rat C6 glioma cell line. During the induction phase the concentration of nuclear mRNALDH sequences increased about 2.5-fold 4 h after the addition of isoproterenol or dibutyryl cAMP. Analysis of nuclear 32P-labeled mRNALDH sequences showed that isoproterenol or dibutyryl cAMP increased the basal rate of in vitro mRNALDH transcription about 3.6-fold within 4 h. The relative rates of in vivo mRNALDH synthesis were additionally measured by pulse-labeling of glioma cells for 15 min with [3H]uridine. The induction of mRNALDH in intact glioma cells by isoproterenol and dibutyryl cAMP was quantitatively comparable to that observed in isolated nuclei and the relative rate of [3H]uridine incorporation into mRNALDH was maximal 4 to 5 h after the initial induction stimulus. Increased synthesis of mRNALDH in vivo as well as in isolated nuclei occurred only at isoproterenol concentrations that caused elevated levels of glioma cell cAMP. Analysis of the kinetics of decay of [3H]uridine-labeled mRNALDH showed a linear rate of decay of non-induced mRNALDH with a t1/2 of 45 min. After isoproterenol stimulation mRNALDH decayed as two populations, one with a t1/2 of 50 min and the other one with a t1/2 of 2.5 h. These results indicate that both isoproterenol and dibutyrl cAMP regulate not only the rate of transcription of mRNALDH but that the stability of mRNALDH is increased during the induction phase.
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PMID:Cyclic AMP regulation of lactate dehydrogenase. Isoproterenol and N6,O2-dibutyryl cyclic amp increase the rate of transcription and change the stability of lactate dehydrogenase a subunit messenger RNA in rat C6 glioma cells. 630 Jan 27


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