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)

A neuroblastoma X Chinese hamster embryonic brain explant hybrid cell line (NCB-20) expressed 5-hydroxytryptamine (5-HT1) receptors, linked to adenylate cyclase, which closely resembled 5-HT1 receptors previously characterized in central nervous tissue. However, the affinity of the receptors for 5-HT was only 150 nM compared to 5 nM in membranes prepared from cerebral cortex. The elevation of cyclic AMP levels in NCB-20 cells produced by 5-HT was found additive to that produced by cholera toxin but synergistic with that produced by either prostaglandin E1 (PGE1) or forskolin, suggesting that these latter two agents elevate cyclic AMP levels by a different mechanism than 5-HT. The elevation of cyclic AMP levels by either 5-HT or PGE1 was reversed by [D-Ala2,D-Leu5]enkephalin (DADLE), morphine, clonidine, and 3,4-dihydroxyphenylethylamine (dopamine) on a short (30 min) time scale. However, continued exposure to DADLE resulted in loss of the initial inhibitory effects of DADLE after 6 h and return of cyclic AMP levels to that seen with either 5-HT or PGE1 alone. When the DADLE exposure time was increased to 48 h, 5-HT produced a further twofold increase in cyclic AMP levels, but there was no increase in the responsiveness of the cells to PGE1 unless naloxone was added 1 h prior to treatment with PGE1. Scatchard analysis showed that the increased potency of 5-HT resulted from an increase in receptor affinity for 5-HT (from a KD of 150 +/- 20 nM to one of 20 +/- 7 nM), with a reduction in the number of apparent binding sites. The 5-HT supersensitivity observed in NCB-20 cells may be a good model for neurotransmitter interactions that produce desensitization or facilitation in the intact nervous system.
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PMID:Evidence for [D-Ala2,D-Leu5]enkephalin-induced supersensitivity to 5-hydroxytryptamine in a neurotumor x brain hybrid cell line (NCB-20). 299 93

The human neuroblastoma cell line designated NMB (Brodeur et al., 1977, Cancer 40: 2256) has been shown to have specific opiate binding sites. These sites are highly stereospecific. Two characteristic delta specific peptides, D-Ala2-D-Leu5 enkephalin and D-Thr2-D-Thr6 enkephalin, have high affinity for the binding sites. Morphine binds specifically but with a much lower affinity. Dextrorphan and the mu specific peptide morphiceptin (Tyr-Pro-Phe-Pro-CO-NH2) do not bind to the site. The binding sites are heat and trypsin sensitive. Sodium ions specifically lower agonist binding to the sites. Approximately 14,000 binding sites per cell are found. The binding characteristics of these sites are very similar to those of the delta sites characterized on mouse neuroblastoma cell lines.
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PMID:NMB: a human neuroblastoma cell line with specific opiate binding sites. 300 Mar 78

Specific binding of [3H][D-Ala2,D-Leu5]enkephalin, [3H]ethylketocyclazocine, 5-[3H]hydroxytryptamine, and [3H]spiperone was examined in neuroblastoma-brain hybrid cell line NCB-20 following exposure to inhibitors of N-linked protein glycosylation (tunicamycin, TM) and oligosaccharide processing (swainsonine, SW). TM treatment reduced ligand binding at delta- and sigma-opiate receptors and neuroleptic binding sites (20 to 50% of control), with no discernible effect on the binding properties of 5HT1-serotonin receptors. In contrast, exposure to SW resulted in a three-fold increase in binding capacity of sigma-receptors, while decreasing receptor affinity for ligand. SW treatment did not alter ligand interactions with either sigma-receptors or neuroleptic binding sites, but did reduce specific binding of serotonin to 5HT1-receptors. The effects of TM and SW on distinct receptor subpopulations were further demonstrated by attenuation of opiate and serotonin-mediated regulation of intracellular cyclic AMP.
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PMID:Differential regulation of multiple neuroreceptors in a somatic cell hybrid by inhibitors of glycoprotein processing. 300 90

A subclone of NG108-15 neuroblastoma-glioma hybrid cells was used to study the intracellular distribution of opioid receptors. Subcellular organelles were separated on self-generating Percoll-sucrose gradients and the enzymes beta-glucuronidase, galactosyltransferase, 5'-nucleotidase, and glucose-6-phosphatase were used as markers to localize the various structures. Analysis of the receptor distribution from untreated cells shows that the plasma membranes contained the highest receptor density, but a significant portion of the opioid binding sites was unevenly distributed between the lysosomes, microsomes, and Golgi elements. The enzyme markers indicated that appearance of opioid receptors in these intracellular structures does not result merely from contamination with plasma membranes. About 11% of the receptors appeared in a fraction lighter than plasma membranes. The antilysosomal agent chloroquine altered the intracellular compartmentation of the receptors, possibly by blocking their translocation in the cells. Leu-enkephalin induced time-dependent loss of receptors from all four intracellular compartments examined, but a kinetic analysis showed that the rate of receptor loss in these fractions was not identical. Thus, the percent of receptors appearing in the lysosomal fraction that could still bind [3H]D-Ala2-D-Leu5-enkephalin in vitro was increased on treatment with Leu-enkephalin. As an additional approach to follow the intracellular fate of the receptors, cells were labeled with [3H]diprenorphine, chased with various unlabeled opiates, and the distribution of 3H-ligand-receptors in the cells was monitored. Leu-enkephalin and etorphine altered the distribution of receptor-bound [3H]diprenorphine between the plasma membranes, lysosomes, and Golgi elements, whereas morphine had no such effect. The study sheds light on the role of intracellular structures in the metabolism of opioid receptors in untreated and opioid-treated cells.
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PMID:Subcellular compartmentation of opioid receptors: modulation by enkephalin and alkaloids. 300 5

Cannabimimetic drugs have been shown to inhibit adenylate cyclase activity in N18TG2 neuroblastoma cells. This investigation examines the possible role of opioid receptors in the cannabimimetic response. Opioid receptors of the delta subtype were found on N18TG2 membranes using [3H]D-Ala2-D-Leu5-enkephalin. No mu or kappa receptors were detected using selective ligands for these sites. The delta binding affinity and capacity were unaltered by cannabimimetic drugs. To test if cannabimimetic drugs may modulate opioid effector mechanisms, cyclic AMP metabolism was determined in intact cells and in membranes. N18TG2 adenylate cyclase was inhibited by the cannabimimetic drugs delta 9-tetrahydrocannabinol and desacetyllevonantradol, and by the opioid agents morphine, etorphine, and D-Ala2-Met5-enkephalinamide. The opioid inhibition was reversed by naloxone and naltrexone; however, the cannabimimetic response was unaffected. Both cannabimimetic and opioid drugs decreased cyclic AMP accumulation in intact cells, but opioid antagonists blocked the response only to the latter. Thus, cannabimimetic effects are observed even though opioid receptors are blocked by antagonist drugs. The interaction between desacetyllevonantradol and etorphine was neither synergistic nor additive at maximal concentrations, suggesting that these two drugs operate via the same effector mechanism. Other neuronal cell lines having an opioid response were also examined. The cannabimimetic inhibition of cyclic AMP accumulation in NG108-15 neuroblastoma X glioma cells was not as great as the response in N18TG2. N4TG1 neuroblastoma cells did not respond to cannabimimetic drugs under any conditions tested. Thus, the cannabimimetic inhibition of adenylate cyclase is not universally observed, and the efficacy of the cannabimimetic response does not correlate with the efficacy of the opioid response.
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PMID:An assessment of the role of opioid receptors in the response to cannabimimetic drugs. 300 17

Receptor subclass recognition properties of affinity-purified rabbit polyclonal anti-idiotypic anti-opiate receptor antibodies in various membrane preparations have been determined. The anti-receptor immunoglobulins significantly decrease binding of 3H-[D-Ala2,-MePhe4,Gly-ol5]enkephalin, a highly selective mu agonist, in rat neural membrane. In the presence of a concentration of the unlabeled ligand sufficient to block existing mu sites, the antibodies compete, to a lesser degree with 3H-[D-Ala2,D-Leu5]enkephalin for delta site occupancy in both rat neural membrane, and neuroblastoma x glioma membrane preparations. The antibodies do not displace 3H-ethylketocyclazocine from rat brain or guinea pig cerebellum.
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PMID:Subclass specificity of anti-idiotypic anti-opiate receptor antibodies in rat brain, guinea pig cerebellum, & neuroblastoma x glioma (NG 108-15). 301 23

Human neuroblastoma SH-SY5Y cells exhibited a heterogeneous population of mu and delta types of opioid binding sites. These specific binding sites displayed the characteristic saturability, stereospecificity and reversibility, expected of a receptor. Scatchard analysis of [3H]-D-Ala2-D-Leu5-enkephalin (DADLE) in the presence of 10(-5) M D-Pro4-morphiceptin (to block the mu receptors) and the competitive displacement by various highly selective ligands yielded the binding parameters of delta sites which closely resemble those of the delta receptors in brain and mouse neuroblastoma clones. Similarly, the high affinity binding of [3H]-dihydromorphine, together with the higher potency of morphine analogues to displace [3H]-naloxone binding established the presence of mu sites. Guanine nucleotides and NaCl significantly inhibited the association and increased the dissociation of [3H]-DADLE binding. The observed heterogeneity of opioid receptors in cultured SH-SY5Y cells would serve as an excellent model for the biochemical and pharmacological characterization of brain opiate receptors.
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PMID:Opioid receptors in human neuroblastoma SH-SY5Y cells: evidence for distinct morphine (mu) and enkephalin (delta) binding sites. 301 31

The adenylate cyclase (AC) of the neuroblastoma-glioma hybrid cells (NG108-15), is generally considered to be a model for the study of the biochemical correlates of opiate tolerance and dependence. However, the naloxone-induced rebound response of adenylate cyclase, described in some recent reports, is much smaller than that originally described by Sharma, Klee and Nirenberg (1975). Possible explanations for these discrepancies are: (1) a marked down-regulation of opioid receptors and tolerance produced by the use of delta agonists or (2) the use of etorphine, a relatively hydrophobic drug which has slower dissociation rates than morphine. To test these possibilities, neuroblastoma-glioma hybrid cells were treated cells with morphine, etorphine, [D-Ala2,D-Leu5]enkephalin (DADLE), [D-Ala2]Leu-enkephalinamide (DALAMID) or vehicle. In addition, some of the cells treated with etorphine were washed with DADLE to replace the etorphine without producing the rebound response of adenylate cyclase prior to the addition of naloxone. The cells treated with morphine, DADLE and DALAMID, and incubated with prostaglandin E1 (PGE1) and naloxone showed a significant rebound of adenylate cyclase when compared with control groups and opiate-treated cells, incubated only with PGE1. In contrast, naloxone did not induce any significant rebound response in cells treated with etorphine unless they were previously washed with DADLE. These results demonstrate that the lack of a rebound response in cells treated with etorphine was due to the slow dissociation rates of the opiate and not to tolerance or to down-regulation of opioid receptors produced by agonists of high intrinsic activity.
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PMID:The adenylate cyclase rebound response to naloxone in the NG108-15 cells. Effects of etorphine and other opiates. 302 77

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.
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PMID:Ni-coupled receptors in cultured neural hybrid cells: cell specificity for dibutyryl cyclic AMP-induced down-regulation but not morphological differentiation. 302 8

The effect of opioids on phosphatidylinositol (PI) turnover to release inositol triphosphate (IP3) as second messenger was examined in mouse neuroblastoma X rat glioma hybrid cells NG108-15 (delta-receptors) and human neuroblastoma cells, SK-N-SH (predominantly mu-receptors). PI turnover can be stimulated in both NG108-15 and SK-N-SH cells by bradykinin and acetylcholine, respectively. In contrast, etorphine, DADL ([D-Ala2,D-Leu5]-enkephalin) and DAGO ([D-Ala2,MePhe4,Gly-ol5]-enkephalin), up to 1 microM concentrations failed to affect PI turnover in both cell lines. These results suggest that IP3 is not likely to serve as second messenger for both mu- and delta-opioid receptors.
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PMID:Phosphatidylinositol turnover in neuroblastoma cells: regulation by bradykinin, acetylcholine, but not mu- and delta-opioid receptors. 302 76


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