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

Opiate, muscarinic, and alpha 2-adrenergic receptors and the Ni-coupled response of adenylate cyclase (AC) inhibition were examined in neuroblastoma X glioma NG108-15 (108 CC15) and neuroblastoma X Chinese hamster brain NCB-20 clonal hybrid cells, induced to differentiate with 1.0 mM dibutyryl cAMP (dBcAMP). Scatchard analysis of binding of the opiate agonist 3H-(D-Ala2,D-Leu5)enkephalin (DADLE) and the antagonist [3H] diprenorphine to dBcAMP-treated NCB-20 cell membranes indicated an 80% reduction in opiate receptor density relative to untreated cells (Bmax = 47 +/- 11 fmol/mg of protein versus 220 +/- 48 fmol/mg of protein), with no change in ligand affinities. Binding of the muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate and the alpha 2-adrenergic agonist [3H]-p-aminoclonidine to dBcAMP-treated NCB-20 membranes was also reduced by 50% and 28%, respectively. In contrast, treatment of NG108-15 cells with dBcAMP did not down-regulate opiate, muscarinic, or alpha 2-adrenergic receptor sites. Opiate and alpha 2-adrenergic receptor sites were not down-regulated in the N18TG2 neuroblastoma clone, the common parent of both the hybrid cells, and the apparent source of these receptors. The C6BU-1 parent of the NG108-15 hybrid showed poor specific binding of all ligands examined. dBcAMP was very potent in inducing opiate receptor site down-regulation of NCB-20 cells, with an ED50 after 4 days treatment of 8 microM. The time course of loss of [3H]DADLE and [3H]quinuclidinyl benzilate specific binding was similar, and maximum down-regulation was achieved after 2 days. In contrast, neither higher concentrations of dBcAMP (5.0 mM) nor longer treatment times (7 days) resulted in down-regulation of receptor sites on NG108-15 cells. Coupling of opiate receptors to AC was also selectively altered in differentiated NCB-20 cells. Prostaglandin E1-stimulated AC was maximally inhibited by 1 microM DADLE in membranes from undifferentiated cells to different degrees (30% in NCB-20 and 54% in NG108-15). dBcAMP treatment had no effect on opiate inhibition of AC in NG108-15 cells but reduced by 50% the maximum opiate inhibition of AC in NCB-20 cells. These data indicate that the signal for receptor down-regulation which was triggered by dBcAMP in the NCB-20 cell comes uniquely from the Chinese hamster brain cell NCB-20 parent. The differences between NCB-20 and NG108-15 cells in the regulation of Ni-coupled receptors provides an example of dBcAMP-induced heterologous down-regulation with unique cell specificity, which is unrelated to the morphological differentiation process triggered by dBcAMP, which is common to both cells.
 ...
PMID:Ni-coupled receptors in cultured neural hybrid cells: cell specificity for dibutyryl cyclic AMP-induced down-regulation but not morphological differentiation. 302 8

Chronic treatment of neuroblastoma X glioma hybrid cells (NG 108-15) with the muscarinic cholinergic agonist carbachol, which acutely inhibits adenylate cyclase, resulted in a 104 +/- 10% increase in PGE1-stimulated cAMP accumulation. Pretreatment of intact cells with pertussis toxin can structurally modify the inhibitory regulatory protein, Gi, by ADP-ribosylation and thus abolish the acute inhibition by carbachol. Pretreatment of the cells with pertussis toxin also resulted in a 27 +/- 8% increase in PGE1-stimulated cAMP accumulation. In the pertussis toxin-treated cells, chronic treatment with carbachol did not further enhance the PGE1 stimulation. These results suggest that functional Gi is required for the development of muscarinic cholinergic-induced enhancement of PGE1-stimulated cAMP accumulation.
 ...
PMID:Muscarinic cholinergic receptor-induced enhancement of PGE1-stimulated cAMP accumulation in neuroblastoma X glioma cells: prevention by pertussis toxin. 302 78

Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.
 ...
PMID:Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP). 303 19

Continuous exposure of rat glioma C6 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a time and dose dependent loss of [3H]phorbol dibutyrate binding sites and protein kinase C activity. Thus, by 24 h, the cells were essentially depleted of protein kinase C activity. In agreement with previous studies, TPA treatment caused a reduction in isoproterenol-stimulated adenylate cyclase activity and a sequestration of beta-adrenergic receptors. Cells were treated with TPA for 24-48 h to completely down-regulate protein kinase C and then exposed to isoproterenol. Agonist-mediated desensitization of adenylate cyclase and sequestration of beta-adrenergic receptors occurred at similar rates in control and TPA-treated cells. In addition, agonist-mediated down-regulation of beta-adrenergic receptors was not impaired by the absence of protein kinase C activity. Although both agonists and phorbol esters cause desensitization of the beta-adrenergic receptor-coupled adenylate cyclase, agonist-mediated events can occur independently of protein kinase C.
 ...
PMID:Down-regulation of protein kinase C in rat glioma C6 cells: effects on the beta-adrenergic receptor-coupled adenylate cyclase. 303 59

Exposure of rat glioma C6 cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) caused an activation of protein kinase C wherein the enzyme rapidly became membrane-bound (T 1/2 of 15 min). This translocation of protein kinase C from cytosol to membrane was followed by a sequestration of cell surface beta-adrenergic receptors and a loss of isoproterenol-stimulated adenylate cyclase activity. We had reported previously that prior exposure of rat glioma cells to concanavalin A prevents the TPA-mediated sequestration of receptors and desensitization of adenylate cyclase (Kassis et al., 1985). We now show that the concanavalin A treatment also prevents the translocation and activation of protein kinase C. These results are further evidence that in the TPA-treated cells, sequestration of beta-adrenergic receptors is mediated by membrane-bound protein kinase C.
 ...
PMID:Concanavalin A prevents phorbol-mediated redistribution of protein kinase C and beta-adrenergic receptors in rat glioma C6 cells. 303 76

The alpha 1 and beta-adrenergic receptor metabolism was studied at cell confluency in BC3H1 and C6 glioma cells. After their irreversible blockade with phenoxybenzamine and a bromoacetyl derivative of pindolol (Br-AAM-pindolol) respectively the receptor reappearance allows to determine a half life of 23 hours for the alpha 1-adrenergic receptor in BC3H1 and a quasi absence of beta-adrenergic receptor metabolism in C6 glioma cells at confluency. In contrast, beta-adrenergic receptor is rapidly synthesized during cell division. This metabolic stability of beta-adrenergic receptor at confluency was also observed in BC3H1 cells using the heavy isotope labeling of the beta-adrenergic receptor (half life of 8 days). This stability was also confirmed by the observation that at confluency in C6 glioma cells, beta adrenergic receptors reappeared at the cell surface after a complete down-regulation. In parallel with the study of the half life of adrenergic receptors, we determined in BC3H1 the half life of the forskolin stimulated catalytic unit of the adenylate cyclase using heavy isotope labeling method. In heavy amino-acid medium the apparent sedimentation coefficients of the adenylate cyclase increased from 7.4 +/- 0.04S (n = 36) to 8.4 +/- 0.03S (n = 13). This increase was due to the synthesis of new heavy molecule since it was blocked by cycloheximide. The analysis of the kinetic of synthesis of heavy molecules allowed to calculate a half life of 36 hours. The comparison between the half life of several regulatory membrane proteins in BC3H1 indicate that each of them has a specific metabolism.
 ...
PMID:Metabolism of adrenergic receptors and adenylate cyclase. 304 Sep 79

Stimulation of basal adenylate cyclase activity in membranes of neuroblastoma x glioma hybrid cells by prostaglandin E1 (PGE1) is half-maximal and maximal (about 8-fold) at 0.1 and 10 microM respectively. This hormonal effect requires GTP, being maximally effective at 10 microM. However, at the same concentrations that stimulate adenylate cyclase in the presence of GTP, PGE1 inhibited basal adenylate cyclase activity when studied in the absence of GTP, by maximally 60%. A similar dual action of PGE1 was observed with the forskolin-stimulated adenylate cyclase, although the potency of PGE1 in both stimulating and inhibiting adenylate cyclase was increased and the extent of stimulation and inhibition of the enzyme by PGE1 was decreased by the presence of forskolin. The inhibition of forskolin-stimulated adenylate cyclase by PGE1 occurred without apparent lag phase and was reversed by GTP and its analogue guanosine 5'-[gamma-thio]triphosphate at low concentrations. Treatment of neuroblastoma x glioma hybrid cells or membranes with agents known to eliminate the function of the inhibitory GTP-binding protein were without effect on PGE1-induced inhibition of adenylate cyclase. The data suggest that stimulatory hormone agonist, apparently by activating one receptor type, can cause both stimulation and inhibition of adenylate cyclase, and that the final result depends only on the activity state of the stimulatory GTP-binding protein, Gs. Possible mechanisms responsible for the observed adenylate cyclase inhibition by the stimulatory hormone PGE1 are discussed.
 ...
PMID:Guanine nucleotide-independent inhibition of adenylate cyclase by a stimulatory hormone. 305 32

Two cDNA clones were obtained from a lambda gt11 cDNA human brain library that correspond to alpha i subunits of G signal-transduction proteins (where alpha i subunits refer to the alpha subunits of G proteins that inhibit adenylate cyclase). The nucleotide sequence of human brain alpha i is highly homologous to that of bovine brain alpha i [Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H. & Numa, S. (1986) FEBS Lett. 197, 305-310] and the predicted amino acid sequences are identical. However, human and bovine brain alpha i cDNAs differ significantly from alpha i cDNAs from human monocytes, rat glioma, and mouse macrophages in amino acid (88% homology) and nucleotide (71-75% homology) sequences. In addition, the nucleotide sequences of the 3' untranslated regions of human and bovine brain alpha i cDNAs differ markedly from the sequences of human monocyte, rat glioma, and mouse macrophage alpha i cDNAs. These results suggest there are at least two classes of alpha i mRNA.
 ...
PMID:Human cDNA clones for an alpha subunit of Gi signal-transduction protein. 311 Jul 83

Although both second messenger response systems are fully functional in both cell lines, activation of muscarinic cholinergic receptors only results in inhibition of adenylate cyclase in NG108-15 neuroblastoma X glioma cells and stimulation of phosphoinositide hydrolysis in 1321N1 human astrocytoma cells. Muscarinic receptors on both cell types were covalently labeled with [3H]propylbenzilylcholine mustard ([3H]PBCM), and the mobilities of the [3H]PBCM-labeled species of both cells were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 1321N1 and NG108-15 cells each primarily expressed a single [3H]PBCM-labeled species with an apparent size of approximately 92,000 and 66,000 Da, respectively. [3H]PBCM labeling was completely inhibited by 1 microM atropine or by down-regulation of muscarinic receptors by an overnight incubation with carbachol. The apparent size of the [3H]PBCM-labeled species of both cell lines was not altered by treatment with a series of protease inhibitors or by treatment with dithiothreitol and iodoacetamide. Since muscarinic receptors are glycoproteins, the contribution of carbohydrate groups to the difference in apparent size of the [3H]PBCM-labeled proteins was determined by treatment of [3H]PBCM-labeled membranes with endoglycosidase F, an enzyme that removes both complex and high mannose type N-linked carbohydrate chains. Endoglycosidase F treatment reduced the apparent size of the [3H]PBCM-labeled species in 1321N1 cells from 92,000 to approximately 77,000 Da and in NG108-15 cells from 66,000 to 45,000 Da. Neuraminidase produced no further reduction of the apparent size of the [3H]PBCM-labeled species from either cell after endoglycosidase F treatment, suggesting the absence of sialic acid containing O-linked carbohydrate chains on the muscarinic receptors of the two cell lines. The results suggest that different muscarinic receptor proteins may be responsible for the two different biochemical responses to muscarinic receptor activation.
 ...
PMID:[3H]propylbenzilylcholine mustard-labeling of muscarinic cholinergic receptors that selectively couple to phospholipase C or adenylate cyclase in two cultured cell lines. 311 80

NG108-15 neuroblastoma x glioma hybrid cells express a major 45 kDa substrate for cholera toxin and a 40 kDa substrate(s) for pertussis toxin when ADP-ribosylation is performed in the presence of GTP. In the absence of exogenous GTP, however, cholera toxin was shown to catalyse incorporation of radioactivity into a 40 kDa protein as well as into the 45 kDa polypeptide. In membranes of cells which had been pretreated in vivo with pertussis toxin, the 40 kDa band was no longer a substrate for either pertussis or cholera toxin in vitro, whereas in membranes from cholera-toxin-pretreated cells the 40 kDa band was still a substrate for fresh cholera toxin in vitro and for pertussis toxin. In this cell line, opioid peptides have been shown to inhibit adenylate cyclase exclusively by interacting with Gi (inhibitory G-protein) and with no other pertussis-toxin-sensitive G-protein. Opioid agonists, but not antagonists, promoted the cholera-toxin-catalysed ADP-ribosylation of the 40 kDa polypeptide, hence demonstrating that this cholera-toxin substrate was indeed the alpha-subunit of Gi. These results demonstrate that Gi can be a substrate for either cholera or pertussis toxin under appropriate conditions.
 ...
PMID:Opioid peptides promote cholera-toxin-catalysed ADP-ribosylation of the inhibitory guanine-nucleotide-binding protein (Gi) in membranes of neuroblastoma x glioma hybrid cells. 313 27


<< Previous 1 2 3 4 5 6 7 8 9 10