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)

Radioligand binding and functional assays were employed to demonstrate the existence of somatostatin receptors in the murine neuroblastoma clone N1E-115. Saturation experiments with [125I][Tyr11]somatostatin-14 indicated the presence of a single class of binding sites in membranes prepared from N1E-115 cells (Kd = 83 pM; Bmax = 21,000 receptors/cell). Somatostatin-14, somatostatin-28 and L363586 (cyclo(N-Me-ALA-TYR-D-TRP-LYS-VAL-PHE] all displaced the 125I-ligand monophasically in N1E-115 cells (Ki values were 28, 82 and 34 pM, respectively), which contrasted with the binding heterogeneity apparent with L363586 in rat brain membranes. The binding of [125I][Tyr11]somatostatin-14 was reduced by GppNHp, indicating that N1E-115 somatostatin receptors interacted with guanine nucleotide binding protein(s). Somatostatin agonists decreased by 30-50% the levels of [3H]cyclic AMP induced in intact cells by forskolin, prostaglandin E1, or vasoactive intestinal polypeptide. The EC50 values for inhibition of the [3H]cyclic AMP response to PGE1 by L363586, somatostatin-14, and somatostatin-28 were 0.24, 0.63 and 1.0 nM, respectively. Pertussis toxin treatment of N1E-115 cells reduced both binding to the receptor and the functional response to somatostatin-14. These data suggest that a single class of somatostatin receptors in N1E-115 cells are linked to the inhibition of adenylate cyclase through a Gi protein.
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PMID:Biochemical evidence for somatostatin receptors in murine neuroblastoma clone N1E-115. 256 62

In IMR32 neuroblastoma cells, the two adenosine receptor agonists N6-R-phenylisopropyladenosine and 5'-N-ethylcarboxamidoadenosine dose-dependently stimulated membrane adenylate cyclase activity with potencies consistent with the presence of adenosine receptors of the A2-subtype. The S enantiomer of N6-R-phenylisopropyladenosine induced a significantly lower stimulation of adenylate cyclase, accordingly to its lower ability to activate adenosine receptors. These effects were selectively counteracted by the adenosine receptor antagonist theophylline and, conversely, were not affected by the A1-adenosine receptor selective blocker 8-cyclopentyl-1,3-dipropylxanthine. No adenosine receptors belonging to the A1-subtype seem, therefore, to be present in this cell line, as also shown by the lack of inhibitory activity of N6-R-phenylisopropyladenosine on both basal and forskolin-stimulated adenylate cyclase activity. Activation of A2-receptors did not modify intracellular basal calcium levels, did not influence calcium influx through voltage-dependent calcium channels and did not modify calcium influx and redistribution induced by muscarinic receptor activation. Prolonged exposure of cells to either N6-R-phenylisopropyladenosine or 5'-N-ethylcarboxamidoadenosine was associated with a small but significant degree of morphological differentiation, comparable to that induced by dibutyryl cAMP, and therefore presumably related to the prolonged increase of intracellular cAMP levels elicited by the two adenosine agonists. After cellular differentiation induced with either dibutyryl cAMP or 5-bromodeoxyuridine, a selective desensitization of A2-receptor stimulated adenylate cyclase activity was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine receptors linked to adenylate cyclase activity in human neuroblastoma cells: modulation during cell differentiation. 277 Oct 50

Opiate receptor-mediated inhibition of adenylate cyclase activity was elicited in membranes of C6BUI glioma cells and S49 cyc- lymphoma cells after fusion with opiate receptor-containing membranes derived from NG108-15 neuroblastoma x glioma hybrid cells. The fusion was induced by polyethylene glycol using procedures developed by Orly and Schramm [(1976) Proc. Natl. Acad. Sci. USA 73, 4410-4414]. Prior to fusion, the adenylate cyclase activity of the donor. NG108-15 cell membrane, was inactivated by N-ethylmaleimide treatment. Prostaglandin E1 receptors and the stimulatory GTP-binding protein Ns were transferred to the recipient cells along with opiate receptors. Thus, inhibitory receptors can be transferred to foreign adenylate cyclase systems just as stimulatory receptors had earlier been found to do. Furthermore, opiate receptors have been shown to function in non-neuronal cells.
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PMID:Transfer of functional opiate receptors from membranes to recipient cells by polyethylene glycol-induced fusion. 282 Aug 7

A previous method of determination of adenine compounds by high-performance liquid chromatography, using bromoacetaldehyde as a fluorescent reagent and a column of Hitachi gel No. 3012-N, was improved and extended to biological materials, especially to measure enzyme activities. A column packed with finer beads, Hitachi gel No. 3013-N, was found to be better than that of No. 3012-N, judging from the analysis time and resolution. ADP, from the hydrolysis of ATP by Na, K-ATPase, was determined quantitatively, and the enzyme activity was inhibited with ouabain. cAMP obtained from ATP by reaction with adenylate cyclase was also determined in the presence of various concentrations of L-epinephrine or sodium fluoride. The ATP levels in human blood were determined, and the cellular levels of ATP and ADP in neuroblastoma N1E 115 were examined as a function of cell growth.
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PMID:Analyses of adenosine and adenine nucleotides in biological materials by fluorescence reaction-high-performance liquid chromatography. 282 41

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

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

The relative capacities of muscarinic cholinergic receptor (MR) and bradykinin (BK)-receptor activation to increase phosphoinositide hydrolysis and to increase cytosolic Ca2+ were compared in NG108-15 neuroblastoma x glioma and 1321N1 human astrocytoma cells. In 1321N1 cells, the muscarinic cholinergic agonist carbachol and BK each stimulated a concentration-dependent accumulation of inositol phosphates (K0.5 approximately 10 microM and approximately 10 nM respectively) and a rapid increase in cytosolic Ca2+ as determined by quin2 fluorescence. In NG108-15 cells, BK alone stimulated a pertussis-toxin-insensitive accumulation of inositol phosphates (K0.5 approximately 10 nM) under conditions in which pertussis toxin completely inhibited MR-mediated inhibition of adenylate cyclase. BK also stimulated a rapid increase in cytosolic Ca2+ in NG108-15 cells. In contrast, no MR-mediated increase in phosphoinositide hydrolysis or change in cytosolic Ca2+ concentration was observed in NG108-15 cells. These results support the idea that MR selectively interact with either the cyclic AMP or the inositol phosphate second-messenger systems.
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PMID:Evidence that muscarinic cholinergic receptors selectively interact with either the cyclic AMP or the inositol phosphate second-messenger response systems. 282 38

1. Nerve growth factor (NGF) induced differentiation of human neuroblastoma cell line. 2. The differentiated cells had a relatively high activity of adenylate cyclase and cyclic AMP phosphodiesterase, and a high intracellular level of cyclic AMP. 3. These cells synthesized a higher amount of met5-o-enkephalin than undifferentiated cells. 4. Undifferentiated cells bound less met5-enkephalin than differentiated cells. The maximum number of [3H]met5-enkephalin receptor sites per mg of membrane protein increased more in differentiated cells. 5. Previous observations taken together with our results suggests that increased intracellular levels of cyclic AMP after treatment with NGF induced differentiation of human neuroblastoma cells. Reversal of undifferentiated tumor cells into the differentiated changes the capacity of synthesis of met5-enkephalin and its interaction with receptors.
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PMID:Nerve growth factor (NGF) induced differentiation of human neuroblastoma cells. 283 Jan 53

Neurotransmitter receptor coupling to adenylate cyclase (AC) was studied in the cultured human neuroblastoma SK-N-MC cell line. Activation of beta-adrenoceptors with isoprenaline (ISO) or vasoactive intestinal polypeptide (VIP) receptors, increased AC activity in a dose-dependent manner. Preincubation with ISO and VIP induced a ligand specific, i.e. homologous type of desensitization of the respective receptor. Neuropeptide tyrosine (NPY) was able to inhibit ISO as well as VIP induced AC activity. The effect of NPY was totally abolished in cells pretreated with pertussis toxin to inactivate inhibitory G-proteins. Thus, SK-N-MC cells possess functionally coupled beta-adrenoceptors, VIP and NPY receptors, and may be used to study interactions between ligands and receptors which couple to the AC system.
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PMID:Beta-adrenoceptor, vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY) receptors functionally coupled to adenylate cyclase in the human neuroblastoma SK-N-MC cell line. 283 76

We investigated the mechanisms of receptor-mediated stimulation of high-affinity GTPase activity in response to opioid peptides and to foetal-calf serum in membranes of the neuroblastoma X glioma hybrid cell line NG108-15. Increases in GTPase activity in response to both of these ligands was abolished by prior exposure of the cells to pertussis toxin. Pertussis toxin in the presence of [32P]NAD+ catalysed incorporation of radioactivity into a broad band of approx. 40 kDa in membranes prepared from untreated, but not from pertussis-toxin-pretreated, cells. Additivity studies indicated that the responses to opioid peptides and to foetal-calf serum were mediated by separate guanine-nucleotide-binding proteins (G-proteins). Whereas opioid peptides produced an inhibition of adenylate cyclase in membranes of untreated cells, foetal-calf serum did not. Affinity-purified antibodies which recognize the C-terminus of the inhibitory G-protein identified a 40 kDa polypeptide in membranes of NG108-15 cells. These antibodies attenuated opioid-stimulated high-affinity GTPase activity, but did not markedly affect the response to foetal-calf serum. We conclude that receptors for the opioid peptides function via the inhibitory G-protein (Gi), whereas foetal-calf serum activates a second pertussis-toxin-sensitive G-protein, which has a C-terminal sequence significantly different from that of Gi.
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PMID:Antibodies which recognize the C-terminus of the inhibitory guanine-nucleotide-binding protein (Gi) demonstrate that opioid peptides and foetal-calf serum stimulate the high-affinity GTPase activity of two separate pertussis-toxin substrates. 283 23


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