Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The attenuation of cyclic AMP accumulation occurs by different mechanisms in 1321N1 astrocytoma cells and NG108-15 neuroblastoma X glioma cells. In 1321N1 cells, cholinergic agonists reduce cyclic AMP accumulation through a Ca2+-dependent activation of phosphodiesterase; in NG108-15 cells, muscarinic receptor-mediated effects on cyclic AMP metabolism occur through inhibition of adenylate cyclase. The goal of the current study was to determine whether different pharmacological specificities were expressed by the muscarinic receptor populations of these two cell lines. The affinity of muscarinic receptors for [3H]quinuclidinyl benzilate (6 pM), [3H]N-methylscopolamine (50 pM), and atropine (80 pM) was similar in membrane preparations from each cell line. The affinity of the antagonist, pirenzepine, which has been proposed to be a selective ligand for a muscarinic receptor subtype, was 3-fold higher in competition binding assays carried out with membranes of 1321N1 cells, than with NG108-15 cells. The Hill coefficients of pirenzepine competition curves were not significantly different from unity in both cell lines. This selectivity of pirenzepine was also apparent in studies of the competitive inhibition of carbachol-induced attenuation of cyclic AMP accumulation in intact cells. Differences in the relative affinities of agonists were observed in competition binding analyses carried out with membranes in the presence of GTP and absence of Mg2+. The Ki values of bethanechol and carbachol were 5- and 12-fold lower for receptors of NG108-15 cells than those of 1321N1 cells and the Ki of methacholine was 3.5-fold lower for 1321N1 cells than for NG108-15 cells. The affinities of oxotremorine and arecoline were similar between the two cell lines. These differences in agonist affinities between the two cell lines were much smaller in analyses of muscarinic receptor-mediated effects on cyclic AMP metabolism in intact cells. Taken together, these data suggest that muscarinic receptors of differing pharmacological specificities regulate cyclic AMP metabolism by different mechanisms in 1321N1 and NG108-15 cells.
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PMID:Muscarinic cholinergic receptors of two cell lines that regulate cyclic AMP metabolism by different molecular mechanisms. 609 92

The effects of the anti-inflammatory and analgesic drug 3-ethyl-1-(3-nitrophenyl)-2,4[1H, 3H]-quinazolindione (TVX 2706) on neuronal and glial cell culture systems including neuroblastoma X glioma hybrid cells have been studied. This compound strongly enhances the increase in intracellular levels of cyclic AMP caused by appropriate effectors in all systems tested so far. EC50 values are in the submicromolar range. The effect is apparently neither due to an increased responsiveness of the hybrid cells for an effector like prostaglandin E1 nor to an increased activity of adenylate cyclase, but to an inhibition of both low and high affinity cyclic AMP phosphodiesterases. Half-maximal inhibition of enzyme activity is obtained at 10 microM TVX 2706. The drug is at least equipotent to or more potent than some other common phosphodiesterase inhibitors. Inhibition of phosphodiesterase activity is also observed in homogenates from rat polymorphonuclear leucocytes, where the low Km-enzyme is preferentially inhibited. TVX 2706 does not interfere with the calmodulin activation of phosphodiesterase. The role of phosphodiesterase inhibition as a possible mechanism of the anti-inflammatory action of TVX 2706 is discussed.
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PMID:TVX 2706--a new phosphodiesterase inhibitor with antiinflammatory action. Biochemical characterization. 609 74

Tyrosine hydroxylase (TH) activity is increased two- to threefold in neuroblastoma cell line NBP2 maintained in culture for 48 h in the presence of either the inhibitor of cyclic AMP-phosphodiesterase (PDE), 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO 20-1724), or the activator of adenylate cyclase, prostaglandin E1 (PGE1). Cyclic AMP levels are elevated 70-80% and 30-40% throughout the 48-h treatment with RO 20-1724 and PGE1, respectively. Carbachol does not affect either basal TH activity or cyclic AMP levels in the cells. However, the cholinergic agonist delays the induction of TH elicited by either RO 20-1724 or PGE1. This delay is prevented by atropine. The elevation in cyclic AMP levels elicited by either RO 20-1724 or PGE1 is blocked for 1 h or 15 min, respectively, after treatment with carbachol. Cyclic AMP levels then begin to rise until they reach those levels observed in the presence of RO 20-1724 or PGE1 alone by 12 h or 1 h of treatment, respectively. Time course studies demonstrate that this transient inhibition of the elevation of cyclic AMP is associated with a 48-h delay in the induction of TH elicited by either RO 20-1724 or PGE1. In contrast, the induction elicited by 8-bromo cyclic AMP is unaffected by carbachol. A depolarizing concentration (56 mM) of KCl produces a 24-h delay in the induction of TH elicited by RO 20-1724, without affecting the concomitant elevation of cyclic AMP produced by the PDE inhibitor. Furthermore, 56 mM-KCl inhibits the induction of TH elicited by 8-bromo cyclic AMP. It thus appears that carbachol delays the induction of TH by transiently inhibiting the elevation of cyclic AMP, whereas potassium depolarization delays the induction of TH by inhibiting a process with a site of action that is distal to the elevation of cyclic AMP.
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PMID:Effect of carbachol and 56 mm-potassium chloride on the cyclic AMP-mediated induction of tyrosine hydroxylase in neuroblastoma cells in culture. 610 63

Cyclic AMP and glucocorticoids appear to have a role in regulating the activity of tyrosine hydroxylase (TH), as well as the expression of "morphological differentiation" in murine neuroblastoma. Monolayer cultures of C-1300 murine neuroblastoma (clone NBP2) were treated with the following compounds in ethanol: dexamethasone, triamcinolone acetonide, hydrocortisone, cortexolone, androstenedione, testosterone, estradiol-17 beta; or with the phosphodiesterase inhibitor Ro20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone]. Treatment with either 200 micrograms/ml Ro20-1724 or 50 micrograms/ml dexamethasone produced significant increases in TH activity compared to alcohol controls (1.44 vs. 0.82 nmol 14CO2/mg protein/hr compared to 0.095). Triamcinolone acetonide or hydrocortisone also produced smaller, but significant, increases in TH activity compared to dexamethasone. When steroid activities were compared at 25 microM concentration and after 60 min of incubation (to maximize TH activity), triamcinolone acetonide was not as effective (62%) as dexamethasone. The relatively inactive glucocorticoid cortexolone produced a slight but significant increase, while the androgens androstenedione and testosterone and the estrogen estradiol-17 beta were without effect.
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PMID:Glucocorticoids increase tyrosine hydroxylase activity in cultured murine neuroblastoma. 611 72

We have demonstrated high affinity diazepam binding sites of the Ro5-4864 benzodiazepine receptor subtype on 108CC15 neuroblastoma X glioma hybrid cells. These cells were previously shown to have purinoceptors of the A2 adenosine subtype and we have now found that [3H]-adenosine can be displaced from this binding site by the benzodiazepines and related compounds that can also bind to the Ro5-4864 site. Diazepam was found to have no intrinsic activity at the A2-receptor as measured by the stimulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production in this cell line. At concentrations sufficient to compete for the A2-receptor, diazepam was shown to facilitate, by approximately 2 fold, the stimulation of cyclic AMP by adenosine. These effects are not due to inhibition of adenosine uptake or phosphodiesterase activity, but are probably a consequence of modulation of the coupling of the A2-receptor to cyclic AMP production in this hybrid cell line.
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PMID:Benzodiazepines modulate the A2 adenosine binding sites on 108CC15 neuroblastoma X glioma hybrid cells. 615 Jul 42

Flat variant clones were isolated from both the N18 neuroblastoma cell line and from a subclone of the parent line exhibiting the typical round cell morphology. Several revertant clones exhibiting the round parental morphology were also isolated from one of the flat variant clones. The flat variants exhibit decreased cloning efficiency in suspension and increased amounts of myosin heavy chain when compared to the round cell clones. Intracellular cAMP levels were increased from two- to fivefold over those in clones representative of the parent line and in the round cell revertants. Treatment with the phosphodiesterase inhibitor RO20-1724 increased cAMP levels and reduced suspension cloning efficiency without altering doubling time or attached cloning efficiency. Increasing cAMP levels of two of the round cell clones by treatment with the phosphodiesterase inhibitor caused increased flattening of the cell body and increased myosin heavy chain content. Thus, even though increased cAMP level may be sufficient to explain the reduced cloning efficiency of the flat variants, it is not the sole cause of the flat morphology.
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PMID:Clonal variation in cultured neuroblastoma cells. II. The relationship of increased intracellular cyclic AMP content to increased anchorage requirement for growth and flattened morphology. 627 18

Nafazatrom (Bay g 6575) was explored for its ability to inhibit platelet aggregation. In vitro, it had no effect on ADP, serotonin, epinephrine, or collagen induced platelet aggregation in platelet rich plasma of monkeys. On the other hand, in vivo it was a powerful inhibitor of ADP induced platelet aggregation as measured by the in vivo platelet aggregation recording instrument described previously (Ambrus et al., 1976). This effect was potentiated by dipyridamole. On the other hand, following parenteral administration of Bay g 6575, no ex vivo inhibition was noticed of ADP, serotonin, epinephrine, and collagen induced platelet aggregation. The hypothesis was presented that Bay g 6575 acts by increasing prostacyclin synthesis and/or release or interferes with its decomposition. This may explain in vivo activity; rapid decomposition may explain inability to demonstrate ex vivo activity. This also explains potentiation by the phosphodiesterase inhibitor dipyridamole. Bay g 6575 also was highly effective as a platelet aggregation inhibitor in monkeys after oral administration. In mice, Bay g 6575 increased circulation time of intravenously injected polyploid Ehrlich ascites tumor cells. In Furth-Wistar rats implanted with Furth-Columbia Wilms' tumor, in A/J mice implanted with C1300 neuroblastoma and in Wistar rats implanted with SMT-2A (Kim) breast cancer, Bay g 6575 significantly reduced spontaneous pulmonary metastasis. On the other hand, no effect was seen in the metastatic rate of NIH renal adenocarcinoma in BALB/cCr mice.
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PMID:Study of platelet aggregation in vivo. IX. Effect of nafazatrom on in vivo platelet aggregation and spontaneous tumor metastasis. 628 24

Adenosine, 2-chloroadenosine and prostaglandin E1 which are known to increase cyclic AMP in neuroblastoma cells potentiated the acetylcholine-induced muscarinic hyperpolarization of the cells without changing the resting membrane potential. The potentiation caused by 2-chloroadenosine was further augmented by Ro 20-1724, a phosphodiesterase inhibitor. A direct intracellular pressure application of cyclic AMP potentiated the muscarinic hyperpolarization without changing the resting membrane potential. Morphine which inhibits adenylate cyclase antagonized 2-chloroadenosine-induced potentiation of the muscarinic hyperpolarization. These results suggest that changes in cyclic AMP level modulate the muscarinic response of neuroblastoma cells.
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PMID:Cyclic AMP-mediated potentiation of muscarinic hyperpolarization in neuroblastoma cells. 632 Sep 77

Morphological differentiation of neuroblastoma cells (NB15) was induced by cAMP effectors in the presence and absence of serine protease inhibitors. In all conditions tested, the percent differentiation was inhibited by protease inhibitors antipain, diisopropylfluorophosphate (DFP), leupeptin, and soybean trypsin inhibitor (SBTI). The level of morphological differentiation obtained in medium containing fetal calf serum was significantly less than the percent differentiation obtained with serum-free medium alone, so serum-free medium was the principal method of induction and comparisons were made to control uninduced cultures or cultures induced with the phosphodiesterase inhibitor R020-1724. Secreted or cell surface caseinolytic protease activity was higher in differentiating cells than in control cultures and was inhibited by the serine protease inhibitors. The effects of the protease inhibitors on growth and differentiation are discussed.
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PMID:The effects of serine protease inhibitors on morphological differentiation of murine neuroblastoma cells (NB15). 632 88

To clarify the functional significance of type IV phosphodiesterase (PDEIV) in neurons and glia cells [3H]rolipram binding and phosphodiesterase (PDE) activity were examined in cytosol and membrane fractions of neuroblastoma N18TG-2 and glioma C6Bu-1 cells. [3H]Rolipram binding was highly observed in cytosolic fractions of N18TG-2 compared to C6Bu-1. Binding was hardly observed in membrane fractions of both types of cells. Rolipram strongly (70%) inhibited the hydrolytic activity of cAMP in cytosolic fractions of N18TG-2. The activity in cytosol fractions of C6Bu-1 was slightly (20%) inhibited by rolipram. These results suggest that PDEIV plays important roles in neurons.
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PMID:[3H]Rolipram binding and phosphodiesterase activity in neuroblastoma N18TG-2 and glioma C6Bu-1. 752 96


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