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)

Islet-activating protein (IAP), one of the pertussis toxins, exerted dual actions on crude membrane preparations from rat C6 glioma cells; an Mr = 41,000 membrane protein was ADP-ribosylated while GTP (and GTP-dependent isoproterenol) activation of membrane adenylate cyclase was enhanced when membranes were incubated with IaP. Both actions of IaP were dependent on the incubation time and the concentrations of NAD and IAP, and were inhibited by nicotinamide; the one action was strictly paralleled by the other in magnitude. Tryptic digestion of the Mr = 41,000 protein was markedly influenced by the presence of guanyl-5'-yl beta-gamma-imidodiphosphate or NaF, the specific ligands of the regulatory component of the adenylate cyclase system. No ADP ribosylation occurred in the membranes prepared from intact C6 cells that had been incubated with IAP, suggesting that the IAP substrate had already been ADP-ribosylated by the intracellular NAD during incubation of the intact cells. Cholera toxin catalyzed ADP ribosylation of other proteins with Mr = 45,000 and 48,000/49,000 (doublet). It is concluded that IAP, added to intact cells or isolated membranes, causes unique modification of the receptor-adenylate cyclase coupling mechanism as a result of ADP ribosylation of the Mr = 41,000 protein which is presumably one of the subunits, other than the cholera toxin substrates, of the guanine nucleotide regulatory component of the cyclase system.
 ...
PMID:ADP ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. 720 Sep 79

The ATP signaling mechanism in neuroblastoma x glioma hybrid NG108-15 cells differentiated by exposure to dibutyryl-cAMP was characterized. In cells loaded with fura-2, ATP rapidly raised the cytosolic Ca2+ concentration ([Ca2+]i); the magnitude of the rise was inversely proportional to the extracellular Na+ concentration. Large increases in cytosolic Na+ concentration, measured with the fluorescent Na+ indicator sodium-binding benzofuran isophthalate, were dose-dependently elicited by ATP. ATP also evoked the entry of ethidium bromide into cells, and this process was inhibited by Mg2+. Inositol-1,4,5-trisphosphate (IP3) generation induced by ATP was totally blocked by removal of extracellular Ca2+, but residual IP3 generation still remained in nondifferentiated cells. In addition, ATP produced a concentration-, time-, and Mg(2+)-dependent biphasic uptake of 45Ca2+. A range of nucleotides and ATP analogues, including CTP, UTP, and GTP, induced only 9-29% of the ATP response. However, adenosine 5'-thiotriphosphate evoked 79% of ATP-induced 45Ca2+ uptake. 45Ca2+ uptake elicited by ATP could be potently blocked by purinoceptor antagonists, but other tested reagents less effectively blocked the action of ATP. When bradykinin was used as an agonist, the [Ca2+]i rise was transient and was insensitive to the extracellular Na+ concentration. Na+ influx, entry of ethidium bromide, and 45Ca2+ uptake were unaffected by bradykinin. Furthermore, bradykinin-evoked IP3 generation was insensitive to extracellular Ca2+. Neither ATP nor bradykinin had any effect on cAMP levels within cells. These data suggest that ATP induces a [Ca2+]i rise in differentiated NG108-15 cells via two distinct Ca2+ influx mechanisms, i.e., a receptor-operated cation channel and pores formed by ATP4-. These mechanisms are distinct from those elicited by bradykinin.
 ...
PMID:Two distinct ATP signaling mechanisms in differentiated neuroblastoma x glioma hybrid NG108-15 cells. 751 80

The effects of non-hydrolyzable guanyl nucleotide analogue GTP-gamma S on CCKB receptor binding in human and guinea-pig cortex, Jurkat T-cells, rat pituitary GH3 cells, rat glioma C6 cells and human small cell lung cancer NCI-H69 cells were investigated by using [3H]CCK-8S saturation and competition binding studies. GTP-gamma S caused inhibition of specific [3H]CCK-8S binding in a concentration dependent manner with a plateau at 10-25 microM. 25 microM GTP-gamma S resulted in a small but significant increase in Kd and IC50 values with amount very similar in all CCKB receptor models tested. However, the maximal number of specific [3H]CCK-8S binding sites (Bmax) was unaffected. Results suggest that CCKB receptors are G-protein coupled in a similar way to human and guinea-pig cortex, Jurkat cells, GH3 cells, C6 cells and NCI-H69 cells.
 ...
PMID:Effects of guanyl nucleotides on CCKB receptor binding in brain tissue and continuous cell lines: a comparative study. 756 15

1. The effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15. 2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells in a concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5-methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR 113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH 23390, and pindolol were completely ineffective against this 5-HT-induced enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced enhancement of cyclic AMP accumulation.8. Chronic treatment with other antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT-induced enhancement of cyclic AMP accumulation.9. Taken together, these results suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor-mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells may result from changes at the level of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase. It is unlikely that this enhancement of cyclic AMP accumulation is caused by long-term antagonism of the 5-HT receptor by amitriptyline.
 ...
PMID:Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic amitriptyline treatment in NG 108-15 cells. 762 Jul 19

Substituted oxoisoindolines are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 16 at both regulatory enzymes, i.e. PRPP amido transferase, IMP dehydrogenase and dihydrofolate reductase. The agent lowered d(GTP) and d(CTP) pool levels, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 16 for 24 hr at 100 microM and some undefined interaction between the drug and the nucleoside bases appeared to occur, lowering DNA synthesis and causing cell death.
 ...
PMID:The cytotoxicity of [(N-alkyl-1H,3H-1-oxoisoindoline-5-yl-oxyl alkanoates and related benzamides in murine and human tissue cultured cell lines. 765 21

Substituted isoindoline-1,3-diones are effective cytotoxic agents, causing cell death in a number of tissue culture lines, e.g. L1210, Tmolt-3, and HeLa-S3. In general these agents were not active against the solid cell growth, i.e. KB, skin, colon, HCT-8 ileum, colon, bronchogenic lung, osteosarcoma and glioma. The mode of action of the derivatives involves inhibition of de novo purine synthesis of Tmolt-3 cells, which reduces DNA and RNA syntheses. Purine synthesis was reduced by compound 4 at both regulatory enzymes, i.e. PRPP amido transferase and IMP dehydrogenase. The agent lowered d(GTP) pools, further reducing DNA synthesis. DNA strand scission was evident after incubation with Compound 4 for 24 hr at 100 microM, lowering DNA synthesis and causing cell death.
 ...
PMID:The cytotoxicity of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]-alkanoic acids in murine and human tissue cultured cell lines. 765 22

When cellular stimulants such as neurotransmitters, hormones, autacoids, cytokines and growth factors stimulate their respective specific receptors in the plasma membranes of cells, a variety of responses are elicited. GTP-binding proteins are also involved in the reactions between receptors and cellular effectors. Stimulation of receptors are subsequently coupled to the activation of ion channels, turnover of inositol phospholipid metabolism, adenylate cyclase and guanylate cyclase, inhibition of adenylate cyclase and potentiation of all proliferation. Active substances such as the so-called second messengers are produced in the cells. In this article, two findings are described: 1) Ca2+, which increases by stimulation of receptors with neurotransmitters and hormones, stimulated Ca2+/calmodulin-dependent protein kinase II in cell systems such as NG108-15 neuroblastoma x glioma hybrid cells and primarily cultured neuronal cells of rat hippocampus. 2) Coupling preferences and possible transduction mechanisms from experiments on NG108-15 cells and NL308 neuroblastoma x fibroblast hybrid cells which have been stably transfected with DNA for m1, m2, m3 and m4 muscarinic acetylcholine receptors were examined. These results may provide a useful research model for examining and evaluating the effects and mechanisms of the drugs on a living system and may help develop useful methodology for the discovery of innovative drugs.
 ...
PMID:[Cellular reactions after stimulation of receptors: research model for evaluation of effects and action mechanisms of drugs for discovery of innovative drugs]. 769 94

The present article investigates chronic opioid regulation of the stimulatory adenylate cyclase-coupled prostaglandin E1 (PGE1) receptor system in neuroblastoma x glioma (NG108-15) hybrid cells. Persistent activation of delta-opioid receptors by morphine (10 mumol/L; 3 days) substantially down-regulates the number of PGE1 binding sites by approximately 30%, without affecting their affinity. Radioligand binding studies performed in the presence of GTP gamma S (100 mumol/L) further revealed that the remaining PGE1 binding sites are still capable of interacting functionally with their associated stimulatory G proteins, Gs. On the postreceptor level, neither changes in the abundance nor in the intrinsic activity of the alpha subunit of Gs (Gs alpha) were found during the state of opioid dependence, as has been verified by western blot and S49 cyc- reconstitution experiments, respectively. Evaluation of the functional interaction between PGE1 receptors and Gs by means of receptor-stimulated, cholera toxin-catalyzed ADP-ribosylation of Gs alpha revealed a significant increase in the ability of PGE1 receptors to activate Gs alpha (3.3-fold increase in EC50; p < 0.05) in cells chronically exposed to morphine. This effect was completely blocked by coincubation of the cells together with the opiate antagonist naloxone (100 mumol/L; 3 days), whereas precipitation of morphine withdrawal by naloxone (100 mumol/L) had no further effect on sensitization in PGE1 receptor/Gs coupling. These findings provide evidence that the stimulatory adenylate cyclase-coupled PGE1 receptor system represents a potential target of chronic delta-opioid receptor activation in NG108-15 hybrid cells. They further suggest that sensitization in stimulatory signal transduction plays a critical role in the generation of opioid dependence.
 ...
PMID:Chronic activation of inhibitory delta-opioid receptors cross-regulates the stimulatory adenylate cyclase-coupled prostaglandin E1 receptor system in neuroblastoma x glioma (NG108-15) hybrid cells. 776 24

The effects of dibutyryl cyclic AMP (dbcAMP) treatment on Ca2+ channel activities, Ca2+ accumulation by intracellular Ca2+ pools, and sizes of IP3- and GTP-releasable pools in neuroblastoma x glioma hybrid NG108-15 cells were studied. High extracellular K+ induced a greater rise in intracellular calcium concentration ([Ca2+]i) in dbcAMP-treated cells than in control cells. In dbcAMP-treated cells, the initial phase of the high K(+)-induced [Ca2+]i rise displayed a much higher sensitivity to omega-conotoxin than it did in control cells, whereas the plateau phase of the [Ca2+]i rise was sensitive only to nifedipine. These results indicate that predominantly L-type Ca2+ channels exist in control cells, and that N-type channels develop only after dbcAMP treatment. In dbcAMP-treated cells, mitochondria showed an increased Ca2+ uptake capacity (5.3 nmol Ca2+/mg protein) compared with that in control cells (4.2 nmol Ca2+/mg protein). However, dbcAMP treatment did not cause significant change in the affinity for Ca2+. Dibutyryl cAMP treatment enhanced the Ca2+ accumulation activity by nonmitochondrial pools (from 0.84 to 0.97 nmol Ca2+/mg protein) and increased the affinity for Ca2+ (EC50 for Ca2+ decreased from 0.146 microM to 0.063 microM). Our data also indicate that the pool that is sensitive to both IP3 and GTP was enlarged. The affinities for IP3 and GTP in causing Ca2+ release remained the same before or after dbcAMP treatment.
 ...
PMID:Enhanced calcium signalling events in neuroblastoma x glioma hybrid NG108-15 cells after treatment with dibutyryl cyclic AMP. 782 5

The coupling efficiencies of beta-1 and beta-2-adrenergic receptors (ARs) in rat C6 glioma cells and the effect of changes in subtype density and ratio caused by dexamethasone (DEX) treatment were studied. Radioligand binding studies in membranes suggested that beta-2-ARs showed slightly larger GTP-induced decreases in agonist affinity than beta-1-ARs, which suggests more ternary complex formation with Gs. Treatment with DEX increased the proportion of beta-2-ARs from 20% to 60% without affecting GTP-induced decreases in agonist affinity. Coupling efficiency was determined directly by progressive inactivation of beta-ARs with the irreversible alkylating agent pindobind, which caused similar reductions in beta-1 and beta-2-AR binding sites. Studies on cyclic AMP accumulation showed that DEX-induced decreases in beta-1/beta-2 ratio reduced the receptor reserve for the beta-1-selective agonist norepinephrine but increased the maximal response to the beta-2-selective agonist zinterol without creating a receptor reserve. DEX treatment did not alter occupancy-response curves or maximal responses to the nonselective agonists isoproterenol and epinephrine. It was concluded that changing beta-2-AR density alters the maximal response to beta-2-AR activation; changing beta-1-AR density alters the apparent beta-1-AR reserve. Both subtypes contribute to the responses to nonselective agonists in a nonadditive manner. Beta-1- and beta-2-ARs appear to couple with different efficiencies (beta-1 > beta-2) to cyclic AMP accumulation in C6 glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Coexisting beta-1 and beta-2-adrenergic receptors with differential receptor reserves in rat C6 glioma cells. 789 20


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