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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormonal regulation of Mg2+ influx was examined in the neuroblastoma X glioma hybrid cell line NG108-15 and the skeletal muscle cell line G8 using 28Mg2+. Both cell lines express multiple classes of hormone receptors; in addition, G8 cells can be induced to differentiate from a single myoblast-like cell into fused myotube-like cells. In NG108-15 cells, 2-Cl-adenosine, an adenosine receptor agonist, stimulated Mg2+ influx by about 60%. This effect was not mimicked by norepinephrine or PGE1, agonists at alpha 2-adrenergic and prostaglandin receptors which NG108-15 cells also express. Carbachol, acting through a muscarinic receptor, gave minimal and variable stimulation of Mg2+ influx. The effect of 2-Cl-adenosine was not blocked by theophylline, an adenosine receptor antagonist, and was not mimicked by adenosine analogs selective for either A1 or A2 adenosine receptors, suggesting that a nonclassical adenosine receptor mediates the effect on Mg2+ influx. Theophylline slightly stimulated Mg2+ influx as did the permeable cyclic AMP analog, 8-Br-cyclic AMP. These results indicate that cyclic AMP may influence Mg2+ influx in NG108-15 cells unlike previous results in murine S49 lymphoma cells [Maguire and Erdos, J. biol. Chem. 255: 1030-1035, 1980] where receptor modulation of Mg2+ influx was independent of cyclic AMP. In G8 cells, the nicotinic cholinergic receptor agonist carbachol stimulated Mg2+ influx at the myoblast cell stage but had no effect on Mg2+ influx after cells had formed myotubes. The beta-adrenergic agonist isoproterenol had the opposite effect, stimulating Mg2+ influx in the myotube stage but not in the myoblast stage. Taken together, these results demonstrate that only a subset of receptors expressed by a cell may be coupled to Mg2+ influx, that the regulation of Mg2+ influx differs from cell type to cell type, and finally, that modulation of Mg2+ influx by hormone receptors may change with differentiation.
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PMID:Hormonal regulation of magnesium uptake: differential coupling of membrane receptors to magnesium uptake. 282 11

Opiate, muscarinic, and alpha 2-adrenergic receptors on NCB-20 and NG108-15 neuroblastoma hybrid cells were up-regulated by treatment of the cells with media (CM) conditioned by previous incubation with either cell type. NG cells treated with CM from both NCB and NG cells (NCB-CM or NG-CM) showed a 2-fold increase in opiate receptor density relative to untreated cells, with no change in ligand affinities. Opiate receptor density on NG cells was also enhanced approximately 2-fold by CM derived from dibutyryl cyclic AMP (dBc)-treated NG cells (NG-dBc-CM) but not by CM from dBc-treated NCB cells, (NCB-dBc-CM). The data suggest that a transferable factor that up-regulates NG opiate receptors is produced by untreated NCB and NG cells, and is either suppressed or inactivated in dBc-treated NCB cells but not in dBc-treated NG cells. Muscarinic and alpha 2-adrenergic receptor site densities on NG cells were also up-regulated approximately 2-fold by NCB-CM but not by NCB-dBc-CM. Thus, the factor induced a heterologous up-regulation of three classes of Ni-coupled receptor sites on NG cells. The up-regulating factor, which accumulates in the media with time in culture, also acts directly upon cells that are synthesizing/secreting the factor (auto-up-regulation). Thus, opiate receptor density increased in untreated NCB and NG cells, as well as in dBc-treated NG cells, as a function of cell growth, but did not increase on dBc-treated NCB cells. Coupling of NG opiate receptors to adenylate cyclase (AC) was not altered by CM. Prostaglandin E1-stimulated AC was maximally inhibited by (approximately 40%) by 1 microM DADLE with the same efficiency and potency in untreated as in CM-treated NG cell membranes. Furthermore, NCB-dBc-CM which does not induce NG opiate receptor up-regulation and NCB-CM, which does induce it, had no effect on inhibition of AC by DADLE. The up-regulating factor is a relatively small molecule (molecular weight = 3000-6000), whose synthesis and/or secretion is suppressed by dBc in NCB but not in the related NG hybrid. This unique cell specificity may be exploited to study the mechanism of opiate, muscarinic, and alpha 2-adrenergic receptor expression and turnover in cultured neural hybrid cells.
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PMID:Heterologous up-regulation of Ni-coupled receptors in cultured neural hybrid cells by a transferable factor, whose expression is inhibited in a cyclic AMP-dependent, cell-specific manner. 282 82

The effects of membrane polyunsaturated fatty acids (PUFA) on opiate peptide-mediated inhibition of basal and prostaglandin E1-stimulated cyclic AMP formation were examined in intact N1E-115 neuroblastoma cells. Addition of opiate peptides such as methionine 5-enkephalin (metEnk) to control cultures and to cultures that had been supplemented for 48 hr with 50 microM linoleic acid resulted in dose-dependent decreases in cAMP formation; these decreases were blocked by naloxone. Maximum inhibition of basal cyclase activity was 50-55% in both control and PUFA-enriched cells; however, half-maximal inhibition required ten times more metEnk in supplemented cultures than in controls. This is consistent with our observation that the affinity of binding of [tyrosyl-3',5'-3H(N)](2-D-alanine-5-D-leucine)enkephalin ([3H]DADLE) to intact PUFA-enriched cells was lower than that to control cells. Receptor density was not modified as a result of supplementation. Addition of prostaglandin E1 (PGE1) to the cells produced rapid dose-dependent increases in cAMP formation. Maximum responses were higher in PUFA-enriched than in control cells (1924 and 972 pmol cAMP formed/mg protein respectively). Also, the apparent value for EC50 for PGE1 was consistently lower in supplemented cultures. MetEnk reduced PGE1-stimulated cAMP formation by 45-55% in both control and supplemented cells, and values for IC50 were similar (approximately 30 nM) in both. In the presence of the opiate peptide, values for EC50 for PGE1 were similar in control and PUFA-enriched cultures (0.07 and 0.09 microM respectively). The data from these studies suggest that membrane PUFA increase the efficiency of coupling of receptors that stimulate cAMP formation and decrease the efficiency of those that mediate inhibition.
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PMID:Effects of membrane polyunsaturated fatty acids on opiate peptide inhibition of basal and prostaglandin E1-stimulated cyclic AMP formation in intact N1E-115 neuroblastoma cells. 282 14

alpha 2-Adrenergic receptors, a population of receptors linked to inhibition of adenylate cyclase, accelerate Na+/H+ exchange in NG108-15 neuroblastoma x glioma cells (Isom, L. L., Cragoe, E. J., Jr., and Limbird, L. E. (1987) J. Biol. Chem. 262, 6750-6757). We now report that two other receptor populations linked to inhibition of adenylate cyclase, muscarinic cholinergic and delta-opiate receptors, also alkalinize the interior of NG108-15 cells, as measured with the pH-sensitive fluorescent probe, 2,7-biscarboxyethyl-5(6)-carboxy-fluorescein. Manipulations that block Na+/H+ exchange, i.e. removal of extracellular Na+, reduction of extracellular pH to equal that of intracellular pH, and addition of 5-amino-substituted analogs of amiloride, all block alpha 2-adrenergic, delta-opiate, or muscarinic cholinergic receptor-induced alkalinization in a parallel fashion. These data suggest that all three populations of receptors alkalinize NG108-15 cells by acceleration of Na+/H+ exchange and do so via a shared or similar mechanism. Although these three receptor populations are linked to inhibition of adenylate cyclase, decreased production of cAMP does not appear to be the mechanism responsible for receptor-accelerated Na+/H+ exchange. Thus, ADP-ribosylation of intact NG108-15 cells with Bordetella pertussis islet-activating protein prevents attenuation of prostaglandin E1-stimulated cAMP accumulation by alpha 2-adrenergic, muscarinic, and delta-opiate agonists but has no measurable effect on the ability of these agonists to accelerate Na+/H+ exchange. Similarly, manipulations that block receptor-accelerated Na+/H+ exchange influence but do not block receptor-mediated attenuation of cAMP accumulation. Thus, the present data suggest that these two receptor-mediated biochemical events, acceleration of Na+/H+ exchange and attenuation of cAMP accumulation, occur through divergent mechanisms in NG108-15 cells.
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PMID:Multiple receptors linked to inhibition of adenylate cyclase accelerate Na+/H+ exchange in neuroblastoma x glioma cells via a mechanism other than decreased cAMP accumulation. 282 23

Upon differentiation with retinoic acid of the human neuroblastoma cells SH-SY5Y into mature neurons, opioid drugs become highly effective in suppressing prostaglandin E1 (50% inhibition)- and forskolin (70% inhibition)-stimulated adenylate cyclase activity, which was assessed by measuring cyclic AMP accumulation in intact cells. Whereas the SH-SY5Y cells carry both mu and delta receptors in a ratio of mu/delta approximately equal to 5/1, the response is predominantly mediated by the mu receptor. Morphine acts as a strong agonist with an EC50 of 50 to 100 nM which falls into the therapeutic range expected for narcotic analgesic effects mediated by the mu receptor. Narcotic analgesic drugs with only partial agonism fail to evoke full response, which suggests that this cell model could provide a rapid screening assay for narcotic analgesic efficacy. Continued exposure of the cells to morphine resulted in partial tolerance within 12 hr with a 4-fold shift of morphine's EC50 to higher concentrations, whereas longer morphine exposure did not cause any further shift. Thus, the differentiated SH-SY5Y cells provide a suitable system for studying the molecular mechanisms of the narcotic analgesics.
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PMID:Efficacy and tolerance of narcotic analgesics at the mu opioid receptor in differentiated human neuroblastoma cells. 283 42

Previous studies have shown that neuroblastoma cells and several types of primary neuronal cells in culture rapidly extend neurites when switched from serum-containing to serum-free medium. The present studies on cloned neuroblastoma cells show that thrombin blocked this spontaneous differentiation at 2 nM with a half-maximal potency of 50 pM. This required the catalytic activity of thrombin and was reversed upon thrombin removal. Thrombin also caused cells in serum-free medium to retract their neurites at equally low concentrations. Two other serine proteases, urokinase and plasmin, did not block or reverse neurite extension even at 100-fold higher concentrations. A specific assay for thrombin indicated that thrombin detected in serum-containing medium from neuroblastoma cultures was derived from serum and that it was likely responsible for much of the known capacity of serum to maintain neuroblastoma cells in a nondifferentiated state. This was supported by the finding that heparin addition reduced the thrombin concentration in serum-containing medium and stimulated neurite outgrowth from neuroblastoma cells in serum-containing medium. Studies on the ability of thrombin to modulate neurite outgrowth by other agents showed that it blocked and reversed the neurite outgrowth activity of two thrombin inhibitors: protease nexin-1 (which is identical to glial-derived neurite-promoting factor) and hirudin. Thrombin, however, did not block the neurite-promoting activity of dibutyryl cAMP or prostaglandin E1. These results suggest a specific role for thrombin in control of neurite outgrowth.
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PMID:Thrombin modulates and reverses neuroblastoma neurite outgrowth. 283 73

Differentiation in the mouse neuroblastoma cells is induced by cAMP and is characterized by neurite extension and increased acetylcholinesterase, cAMP-phosphodiesterase, and RI cAMP-binding activities. To gain a better understanding of the regulation of expression and the possible function of the RI cAMP-binding protein in neuroblastoma cell differentiation, we evaluate the specificity of action of cAMP analogues and agents that increased intracellular cAMP concentration in the induction of the 47,000-dalton RI protein. The amount of RI in cell extracts was quantitated by the photoactivated incorporation of 8-N3-[32P]cAMP into the 47,000-dalton RI and by ELISA and Western blot techniques. Our results showed that dibutyryl cAMP, forskolin, prostaglandin E1, 3-isobutyl-1-methyl xanthine, and papavarine gave a 2- to 4-fold increase in the RI cAMP-binding protein coincident with the expression of various morphological and biochemical differentiation phenotypes in the mouse neuroblastoma cells. However, the effects of 8-bromo-cAMP were different. 8-Bromo-cAMP effectively promoted neurite extension and increased acetylcholinesterase and cAMP-phosphodiesterase activities; however, there was no concomitant increase in the RI cAMP-binding protein. The result raises interesting questions concerning the coupling of expression of the various differentiation phenotypes in the mouse neuroblastoma cells.
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PMID:Specificity of the action of cAMP agonists in the induction of RI cAMP-binding protein in mouse neuroblastoma cells. 283 19

One of the biochemical results of ethanol exposure is a change in the amount of the intracellular second messenger cyclic AMP (cAMP) produced in response to receptor stimulation. In general, acute ethanol exposure increases the amount of cAMP produced on stimulation of receptors coupled to the enzyme adenylyl cyclase via the GTP-binding protein Gs, whereas chronic ethanol exposure has the opposite effect (results for receptors coupled via Gi have been more variable). We previously reported that adaptation to continuous ethanol exposure reduces receptor-stimulated cAMP production by 25-35% in a neuroblastoma cell line (NG108-15), and an even greater reduction of 75% was observed in lymphocytes taken from actively-drinking alcoholics. This reduction in receptor-stimulated cAMP levels was recently confirmed in platelets from alcoholics. None of these studies, however, determined whether more than one receptor coupled to adenylyl cyclase activity was affected in the same cell. Here we report that chronic ethanol exposure causes desensitization of heterologous receptors coupled to Gs as cAMP production mediated by prostaglandin E1 as well as by adenosine is reduced by approximately 30% in NG108-15 cells. We show that, after chronic ethanol exposure, the activity of the alpha subunit of Gs is decreased by 29%, the amount of alpha s protein is decreased by 38.5%, and alpha s messenger RNA is decreased by 30%. Thus, cellular adaptation to ethanol involves a reduction in alpha s mRNA and, as a consequence, reduced cAMP production by heterologous receptors coupled to Gs. Such changes in cAMP production may account for the tolerance and physical dependence on ethanol in alcoholism.
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PMID:Chronic ethanol causes heterologous desensitization of receptors by reducing alpha s messenger RNA. 283 57

To determine the role of adenosine 3'5'-cyclic monophosphate (cAMP) in the antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1), we studied 2 cell lines of human neuroblastoma; i.e. GOTO and SK-N-DZ. PGE1 or E2 at 30 micrograms/ml and PGD2 or PGA1 at 5 micrograms/ml were cytotoxic to these neuroblastoma cells. In both cell lines, increase of intracellular cAMP was closely associated with E-type PGs cytotoxicity, however, in PGD2, or PGA1 cytotoxicity, cAMP increase was observed only in GOTO cells. Pretreatment of GOTO cells with 5 micrograms/ml PGE2 for 24 hr caused a desensitization of cAMP responses to PGE1, PGD2 or PGA1 only in association with a reduced cytotoxicity of PGE1. On the other hand, PGE2-pretreated SK-N-DZ cells resulted in a desensitization in response to PGE1, but not to other PGs, without affecting the cytotoxicity of these PGs. A decreased [3H]PGE1 binding similarly occurred in either the PGE2-pretreated GOTO or SK-N-DZ cells. However, cholera toxin- or forskolin-induced cAMP production was suppressed only in the pretreated GOTO cells. cAMP response by forskolin rather increased in the pretreated SK-N-DZ cells. These results indicate that antineoplastic effect of E type PGs mediates through cAMP, but not that of PGD2 and PGA1 and that PGE2 pretreatment may cause a down regulation of PGE1 receptor site in both cell lines. It is also suggested that PGE2 pretreatment results in a heterologous desensitization in GOTO and a homologous desensitization in SK-N-DZ cells.
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PMID:Role of adenosine 3'5'-cyclic monophosphate in antineoplastic effect of prostaglandins (PGE1, PGE2, PGD2 and PGA1) on human neuroblastoma cells. 284 1

Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 microM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an IC50 of 450 microM. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki value of 162 microM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1-stimulated [3H]cyclic AMP formation was not affected. The Ki for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 microM. Caracemide was a competitive inhibitor of acetylcholinesterase with a Ki value of 8 microM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E-115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system.
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PMID:Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115). 287 11


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