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 effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D-penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13) on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands all elicited dual effects. Low concentrations (< nM) usually elicited a transient increase in IK (within 1 min), followed by a sustained decrease in IK. In contrast, microM concentrations rapidly elicited a sustained increase in IK. After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained decrease in IK evoked by < nM opioid agonists no longer occurred. Low concentrations then elicited only a sustained increase in IK. On the other hand, after chronic treatment with pertussis toxin (PTX), the usual microM opioid-induced increases in IK no longer occurred and more than half of the cells responded with a sustained decrease of IK to microM as well as nM opioids. The results suggest that mu, delta and kappa opioid receptors are each coupled to K+ channels through CTX-B- and PTX-sensitive transduction systems. Both systems have similar threshold concentrations to opioids. Activation of the CTX-B-sensitive opioid receptor/transduction system resulted in a decrease in K+ conductance of the cell which is generally associated with an increase in neuronal excitability. Activation of the other system resulted in an increase in K+ conductance which will, in general, decrease neuronal excitability. The net change in the IK depends upon which effect predominates. The dominance at different opioid concentrations may depend on the relative efficacies of the coupling of these two systems to K+ channels.
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PMID:Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells. 857 91

Using delta opioid receptor as a model system, acute desensitization of neuronal opioid receptor was studied in detail in neuroblastoma x glioma NG108-15 cells and primarily-cultured mouse cortical cells. The opioid desensitization could occur in as short as 3 minutes of agonist treatment and the half-life of the desensitized state was about 90 minutes. This acute opioid desensitization was homologous in nature in both neuronal cells. The acute desensitization was almost abolished by treatment of the neuronal cells with staurosporine, a nonspecific protein kinase inhibitor. Treatment with the protein kinase C-selective inhibitor, calphostin C, however, caused partial block. In conclusion, neuronal opioid receptor undergoes acute, agonist-dependent, and homologous desensitization, during which protein kinases appear to play an important role.
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PMID:delta Opioid receptor in neuronal cells undergoes acute and homologous desensitization. 860 89

We determined the effects of all-trans retinoic acid (RA) on the levels of delta opioid receptor (DOR) mRNA and N-Methyl-D-Aspartate receptor (NMDAR1) mRNA in neuroblastoma x glioma hybrid cells (NG108-15) by use of quantitative solution hybridization assays. The assays utilized riboprobes complementary to major portions of the coding region of the DOR and NMDAR1 cDNAs. At 10 microM RA a 3-fold increase in DOR mRNA at 48 h, and later (144 h) alterations were observed in NMDAR1 mRNA levels. Northern blot analysis revealed six transcripts for DOR mRNA ranging in size from 8.7 to 2.0 Kb, and three transcripts for NMDAR1 mRNA ranging in size from 4.1 to 3.5 Kb. Neither the size nor the fractional band intensity was affected by RA treatment. The delayed induction of DOR mRNA suggests an indirect mechanism by which RA acts on transcription of this gene. A surprising induction of DOR mRNA by the protein synthesis inhibitor cycloheximide (CHX) suggests that either a repressor molecule or degrading enzymes/proteases may regulate basal levels of this mRNA. Treatment with RA resulted in a concentration- and time-dependent morphological differentiation characterized by increased size of the cell body and the appearance of numerous short and long processes.
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PMID:Retinoic acid-induced increase in delta-opioid receptor and N-methyl-D-aspartate receptor mRNA levels in neuroblastoma x glioma (NG108-15) cells. 886 97

NG108-15 neuroblastoma cells differentiated with 0.1 M of all-trans retinoic acid (RA) were processed for immunohistochemical analysis using polyclonal antisera against the delta opioid receptor (DOR) and the N-Methyl-D-Aspartate receptor (NMDAR1) to determine the cellular sites for possible functional associations between DOR and NMDAR1 receptors. In this study, 6 days of RA treatment resulted in prominent morphological differentiation characterized by the appearance of numerous axon- and dendrite-like processes and formation of networks between the cell clusters. An immunocytochemical approach allowed the demonstration of antibody concentration-dependent differences, not evident in ligand binding studies, in the distribution of DOR and NMDA receptor protein between cell soma and processes. RA-differentiated cultures showed positive DOR-like immunostaining (DOR-LI) throughout the cell bodies as well as on the newly acquired processes. In contrast, NMDAR1-like immunoreactivity (NMDAR1-LI) in the RA-treated cells was detected in the cell soma and processes only with the higher concentration of the antiserum. With the lower concentration of the antibody the NMDAR1-LI was not detected in the processes and was limited to a punctuate subcellular distribution in the soma. The DOR-LI pattern of distribution in NG108-15 cells differentiated with RA appeared to be consistent with the DOR-LI detected in the CNS. The NMDAR1-LI distribution in these cells is similar to brain tissue with respect to its presence on the newly acquired processes. However, it differed from brain in that a much higher abundance of NMDAR1 receptors was observed in the cell soma. This differential distribution of DOR and NMDAR1 receptors in the RA-treated NG108-15 cells could provide a basis for future studies of drug-induced changes in these two receptors.
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PMID:Detection of delta opioid receptor and N-methyl-D-aspartate receptor-like immunoreactivity in retinoic acid-differentiated neuroblastoma x glioma (NG108-15) cells. 898 Dec 41

Neuroblastoma x glioma NG108-15 hybrid cells have been examined for the expression of opioid receptor-like receptor (ORL1). [3H]Nociceptin/orphanin FQ (OFQ) bound to the cell membrane specifically (Kd = 3.6 +/- 0.6 nM) and inhibited forskolin-stimulated cAMP accumulation (EC50 = 0.72 +/- 0.3 nM). The responsiveness of NG108-15 cells to nociceptin/OFQ was blocked by pertussis toxin but not by naltrindole. The inhibitory activity of nociceptin/OFQ was significantly reduced after a prechallenge with the same peptide but was not influenced by DPDPE pretreatment, indicating acute and homologous desensitization of ORL1 receptors. Naltrindole caused the overshoot of cAMP in DPDPE-pretreated cells but not in nociceptin/OFQ-pretreated cells. The results indicate that ORL1 is functionally expressed and does not cross-interact with specific ligands of the delta opioid receptor in NG108-15 cells.
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PMID:Functional expression, activation and desensitization of opioid receptor-like receptor ORL1 in neuroblastoma x glioma NG108-15 hybrid cells. 903 67

The wild-type delta opioid receptor (DOR) and a carboxyl terminus-truncated mutant DOR lacking the last 31 amino acids (DOR-T) were expressed in neuroblastoma x glioma hybrid NG108-15 cells to investigate the role of the carboxyl terminus of DOR in agonist-dependent receptor phosphorylation. Stimulation of the cells with delta specific agonists significantly induced DOR phosphorylation whereas no phosphorylation of DOR-T was detected under the same conditions. Neither overexpression of G protein-coupled receptor kinases (GRK2 or GRK5) nor activation of protein kinase C promoted agonist-induced phosphorylation of DOR-T, in contrast to their strong stimulatory effect on the agonist-dependent phosphorylation of DOR. Furthermore, DOR-T failed to be internalized after agonist stimulation, probably due to its inability to be phosphorylated. Our results indicate that the carboxyl terminus of DOR is required for agonist-dependent receptor phosphorylation and the phosphorylation site(s) of DOR is likely located at its carboxyl terminus.
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PMID:Carboxyl terminus of delta opioid receptor is required for agonist-dependent receptor phosphorylation. 929 54

In this study we employed the neuroblastoma x glioma NG 108-15 cell line as a model for investigating the effects of long-term activation of cannabinoid receptors on delta opioid receptor desensitization, down-regulation and gene expression. Exposure of NG 108-15 cells to (-)-delta9-tetrahydrocannabinol (delta9-THC) reduced opioid receptor binding, evaluated in intact cells, by approximately 40-45% in cells exposed for 24 h to 50 and 100 nM delta9-THC and by approximately 25% in cells exposed to 10 nM delta9-THC. Lower doses of delta9-THC (0.1 and 1 nM) or a shorter exposure time to the cannabinoid (6 h) were not effective. Down-regulation of 6 opioid receptors was not observed in cells exposed for 24 h to pertussis toxin (PTX) and then treated for 24 h with 100 nM delta9-THC. In cells that were exposed for 24 h to the cannabinoid, the ability of delta9-THC and of the delta opioid receptor agonist [D-Ser2, Leu5, Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was significantly attenuated. Prolonged exposure of NG 108-15 cells to 100 nM delta9-THC produced a significant elevation of steady-state levels of delta opioid receptor mRNA. This effect was not observed in cells pretreated with PTX. The selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited by delta9-THC on delta opioid receptor desensitization, down-regulation and gene expression; thus indicating that these are mediated via activation of cannabinoid receptors. These data demonstrate the existence, in NG 108-15 cells, of a complex cross-talk between the cannabinoid and opioid receptors on prolonged exposure to delta9-THC triggered by changes in signaling through Gi and/or G0-coupled receptors.
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PMID:Regulation of delta opioid receptors by delta9-tetrahydrocannabinol in NG108-15 hybrid cells. 977 17

The potential modulation of opioid receptor signaling by kainic acid (KA) has been investigated in neuroblastoma x glioma NG 108-15 hybrid cells and neuroblastoma SK-N-SH cells. Acute incubation of KA significantly attenuated delta opioid receptor (DOR) signaling induced by the DOR agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE), as measured by activation of G proteins and inhibition of cAMP accumulation. The attenuation by KA was time- and dose-dependent and could be blocked by antagonists of kainate/AMPA receptors, suggesting possible mediation through kainate/AMPA receptors. KA attenuation of DPDPE-stimulated G protein activation was reversed by inhibitors of protein kinase C or by removal of both extracellular Ca2+ and intracellular Ca2+. In contrast, NMDA attenuation of DPDPE-stimulated G protein activation was independent of intracellular Ca2+, indicating that different mechanism(s) may underlie the modulation effect of KA and NMDA. This notion was further supported by the results that KA did not alter nociceptin/orphanin FQ-stimulated G protein activation in NG 108-15 cells but NMDA did. In addition, pretreatment of NG 108-15 cells with antagonists of kainate/AMPA receptors blocked the acute desensitization of DOR signaling. These data provide evidence that KA may be involved in the modulation of opioid receptor signal transduction.
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PMID:Attenuation of delta opioid receptor-mediated signaling by kainic acid in neural cells: involvement of protein kinase C and intracellular Ca2+. 1042 17

delta Opioid receptors were identified in human melanomas by RT-PCR and radioligand binding. In all tumors an additional PCR amplificate was detected in which 144 bp within the third exon were deleted. This fragment corresponded to the third cytoplasmic domain of the receptor protein. The short variant resulted from atypical mRNA processing. There were no common splice recognition sequences around the deleted fragment; instead its excision resembled the removal of a transposon. The deletion was not detected in normal human melanocytes nor in human or rat brain. However, it was present in a human neuroblastoma cell line (SH-SY5Y). Thus, it appears that the occurrence of the short delta opioid receptor is correlated to malignancy.
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PMID:A delta opioid receptor lacking the third cytoplasmic loop is generated by atypical mRNA processing in human malignomas. 1103 19

In addition to the established human delta opioid receptor SH-SY5Y neuroblastoma cells produce an atypical, shorter, form of this receptor which is predicted to lack the third intracellular domain. Hence it will be referred to as hdelta(deltaICD3). Notably, in unaltered human brain tissue only the established ('wild type') delta receptor was detected. After transfection of the human wild type delta receptor (hdelta(wt)) into NG 108-15 rodent neuroblastoma-derived cells, HEK 293 human embryonic kidney cells and NIH 3T3 mouse fibroblasts, all these cell types produced hdelta(deltaICD3). Only the human but not the rat delta opioid receptor was processed, arguing for a high sequence selectivity of the cleavage process. Upon agonist stimulation hdelta(deltaICD3) was not able to activate potassium channels (K(ir)3.1/K(ir)3.4) expressed in Xenopus laevis oocytes. However, hdelta(deltaICD3) dose-dependently inhibited the signaling of hdelta(wt) if co-expressed with the latter. Thus, hdelta(deltaICD3) can be produced by many cell types and, once produced, markedly interferes with normal delta receptor signaling.
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PMID:A truncated delta opioid receptor, spontaneously produced in human but not rat neuroblastoma cells, interferes with signaling of the full-length receptor. 1278 22


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