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)

In the mouse neuroblastoma x dorsal root ganglion hybrid cell line F-11, bradykinin receptor stimulation induced the release of inositol-1,4,5-trisphosphate (IP3) and inositol-1,4-bisphosphate (IP2). Maximal stimulation of [2-3H]IP3 and [2-3H]IP2 release by bradykinin in the absence of LiCl occurred at 7 (or less) and 15 s, respectively, with average levels of 5.7-(IP3) and 3.4-(IP2) fold of control values. The EC50 for bradykinin was 33 +/- 5 nM. IP3 and IP2 concentrations returned to basal levels approximately 1 min after bradykinin addition. Bradykinin-induced IP3 release was blocked by several novel bradykinin analogues. In particular, [D-Arg0]-Hyp3-Thi5,8-[D-Phe7]-bradykinin [Hyp, hydroxyproline; Thi, beta-(2-thienyl)-L-alanine] blocked IP3 production in a dose-dependent fashion. Several of these analogues alone showed little or no agonist activity. The bradykinin receptor may be coupled to phospholipase C via a GTP-sensitive protein (Gi or Go), as preincubation for 18-20 h with pertussis toxin decreased IP3 concentrations by 45%. Bradykinin is also known to modulate the concentrations of other second messengers in neurons, increasing the concentrations of Ca2+, diacylglycerol (DG), and cyclic GMP and decreasing the concentration of cyclic AMP. These second messengers modulated bradykinin-dependent IP3 release to varying degrees. A23187, a Ca2+ ionophore, produced a 37% decrease in IP3 concentration. 12-O-Tetradecanoylphorbol-13-acetate, which mimics the effects of DG and activates protein kinase C, inhibited IP3 release by 80%. Dibutyryl cyclic GMP produced little or no inhibition of IP3. [D-Ala2,D-Leu5]Enkephalin (DADLE), an opioid peptide that decreases cyclic AMP concentrations, likewise had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of bradykinin-induced inositol trisphosphate release in a novel neuroblastoma x dorsal root ganglion sensory neuron cell line (F-11). 349 4

In mouse neuroblastoma x Chinese hamster brain clonal cell line NCB-20, bradykinin (BK) receptor stimulation causes phosphoinositide hydrolysis and release of inositol phosphates. Maximum stimulation (4-fold) of [2-3H]inositol trisphosphate (IP3) release in the absence of Li+ from NCB-20's prelabelled for 20-24 hours with [2-3H]myo-inositol (15 microCi/confluent 60mm dish) occurred after 5-10 seconds of bradykinin exposure, with an EC50 of approximately 100nM. Inositol bisphosphate (IP2) and inositol monophosphate (IP1) also showed increases (2.9-fold and 1.5 fold, respectively), with peaks at 15-20 seconds and 50 seconds, respectively. Under these same conditions, D-Ala2-D-Leu5 enkephalin (DADLE) (10 microM), an opiate agonist with 2nM affinity, gave no stimulation of IP3 release. Furthermore, it did not block BK-initiated release, both when applied simultaneously with BK and when cells were preincubated with DADLE for 100 minutes to lower cyclic AMP levels. These results show that pain-inducing BK has a major acute stimulatory effect on receptor-phospholipase C-coupled IP3 release, the opioid peptide DADLE has no such effect and, DADLE does not block the IP3 release induced by BK.
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PMID:Bradykinin induces a rapid release of inositol trisphosphate from a neuroblastoma hybrid cell line NCB-20 that is not antagonized by enkephalin. 351 43

Regulation of cellular content of the endogenous opioid peptides Met5-enkephalin and Leu5-enkephalin was investigated in neuroblastoma X glioma hybrid cells NG108-15 grown in both serum-supplemented and serum-free defined media. Untreated cells and cells induced to differentiate were stained using anti-Met5-enkephalin and anti-Leu5-enkephalin with the peroxidase-antiperoxidase immunocytochemical technique at the light microscopic level. In untreated NG108-15 cells grown in serum-supplemented medium, intense enkephalin-like immunoreactivity was localized in cell bodies and short processes of a select population of cells. The volume fraction of stained untreated cells remained constant throughout the time period investigated. When cells were induced to differentiate with N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate (dBcAMP) or 8-bromo cyclic adenosine monophosphate (1.0 mM) treatment for 5 days, staining was found throughout the cytoplasm of perikarya and the extensive processes which were expressed, and the volume fraction of stained cells increased over 2-fold. Receptor-mediated stimulation of adenylate cyclase by prostaglandin E1 (10 microM) for 5 days produced results similar to those with dBcAMP. Pure cultures of differentiated cells with intense staining were obtained by further treatment of cultures, grown in the presence or absence of dBcAMP, with arabinosylcytosine (araC). Untreated, dBcAMP-treated and araC-treated NG108-15 cells grown in defined medium expressed staining patterns and volume fractions of stained cells similar to those grown in serum-supplemented medium; sodium butyrate (1.0 mM), however, increased the volume fraction of stained cells grown in defined medium over 3-fold, whereas it had little effect on staining of cells grown with serum. The presence of both Met5- and Leu5-enkephalin-like activities in NG108-15 cells was confirmed in acid extracts of cells by radioreceptor assay after separation by reverse phase high pressure liquid chromatography. Induction of differentiation in NG108-15 cells by dBcAMP treatment increased the cellular concentration of both enkephalins to over 2 times the levels found in untreated cells. The biochemical analysis for Met5-enkephalin- and Leu5-enkephalin-like activity compared well with the immunocytochemical data indicating that the enkephalin content is correlated with the state of differentiation of NG108-15 cells.
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PMID:Induction of differentiation increases Met5-enkephalin and Leu5-enkephalin content in NG108-15 hybrid cells: an immunocytochemical and biochemical analysis. 619 53

The binding of many opiates and enkephalins to enkephalin (delta) and morphine (mu) receptors was compared by using three different binding assays: (i) 125I-labeled[D-Ala2, D-Leu5]enkephalin or 125I-labeled[D-Ala2,N-Me-Phe4,Met(O)5ol]-enkephalin to brain membranes; (ii) [3H]ethylketocyclazocine to brain membranes; and (iii) [3H]diprenorphine and [3H]naloxone to neuroblastoma cell and brain membranes, respectively. According to their relative binding potencies and the effects of Na+ and GTP on the binding to these two receptors, opiates and enkephalins can be classified into seven classes: (i) morphine-type mu agonists; (ii) enkephalin-type delta agonists; (iii) mixed agonists-antagonists; (iv) putative kappa agonists; (v) putative sigma agonists; (vi) nalorphine-type antagonists; and (vii) opiate antagonists. Studies with [3H]ethylketocyclazocine do not reveal specific kappa receptors distinct from those already described that bind morphine and enkephalins. The benzomorphan analogs ketocyclazocine and ethylketocyclazocine (putative kappa agonists) and N-allylnormetazocine (putative sigma agonist) bind to morphine (mu) and enkephalin (delta) receptors with similarly high affinities. The potency of putative kappa agonists, measured by competition with binding of the 3H-labeled antagonist, is greatly reduced by the presence of Na+ and GTP; the "Na+ and GTP ratios" are similar to those of morphine and enkephalins. However, Na+ and GTP greatly decrease the potency of binding of putative sigma agonists to enkephalin receptors but only slightly decrease the binding to morphine receptors. These data suggest that putative kappa agonists have agonistic activity toward both receptors, whereas putative sigma agonists behave as agonists for enkephalin receptors but have antagonist activity for morphine receptors. Mixed agonist-antagonists also show smaller difference in affinity to both receptors. These findings may have important implications for understanding the differences in the pharmacological effects of these drugs.
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PMID:Possible role of distinct morphine and enkephalin receptors in mediating actins of benzomorphan drugs (putative kappa and sigma agonists). 625 28

Exposure of mouse neuroblastoma cell line N4TGl to opiates or [D-Ala2,D-Leu5] enkephalin produced a naloxone-reversible inhibition of cyclic AMP synthesis and prevented, in a concentration-dependent manner, the formation of both ganglioside GM2 (GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM3 (NeuNAc-Gal-Glc-ceramide) and ganglioside GM1 (Gal-GalNAc-[NeuNAc]-Gal-Glc-ceramide) from GM2 in cell-free extracts. In contrast, the receptor-mediated elevation of intracellular cyclic AMP levels by agents such as prostaglandin E1 (in the presence of isobutylmethylxanthine) or the addition of the cyclic AMP derivatives (dibutyryl cyclic AMP) markedly stimulated the activities of UDP-GalNAc:GM3,N-acetylgalactosaminyltransferase and UDP-Gal:GM2,galactosyltransferase. An overall increase in the synthesis of gangliosides more complex than GM3 was also observed in the mouse neuroblastoma x hamster brain explant hybrid cell line NCB-20 following elevation of cyclic AMP levels by treatment with serotonin and pargyline. The data presented support the hypothesis that cyclic AMP may have a role in the regulation of sialoglycosphingolipid biosynthesis.
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PMID:Possible role of cyclic AMP in the receptor-mediated regulation of glycosyltransferase activities in neurotumor cell lines. 626 98

The association of [3H] [D-Ala2, D-Leu5] enkephalin ([3H]DADLE]) with mouse neuroblastoma cells (N4TG1) was investigated. Under identical conditions the time course, dose response curve and temperature dependence for ligand uptake were similar to those for ligand-induced receptor loss (down regulation). Uptake of [3H]DADLE was inhibited by opiate ligands as well as by the metabolic inhibitors sodium azide and 2,4 dinitrophenol. Comparison of the effects of these inhibitors on receptor binding, ligand uptake and receptor loss indicated that these cells accumulate [3H]DADLE in excess of their surface receptor number. The data suggest that receptor recycling occurs and that ligand is internalized via receptor mediated endocytosis.
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PMID:Studies on the mechanism of enkephalin receptor down regulation. 629 20

A dimeric pentapeptide enkephalin (DPE2) consisting of two molecules of [D-Ala 2, Leu 5] enkephalin linked at C-terminal leucine with ethylenediamine, (H-Tyr-D-Ala-Gly-Phe-Leu-NH-Ch2)2 is a bivalent ligand for the delta enkephalin receptors of rat brain and neuroblastoma-glioma hybrid (NG108-15) cells. This new enkephalin analog shows dramatically increased affinity in radioligand assays using whole brain membranes when delta but not mu specific radioligands are employed. When membranes from NG108-15 cells are used, the dimer shows greatly increased activity irrespective of the mu or delta specificity of the tracer. The dimer DPE2 shows a four-fold, "sodium shift" in its IC50 for competition with [3H]naloxone, suggestive of agonist behavior. Agonist activity was confirmed by demonstrating that DPE2 inhibits cyclic AMP production in prostaglandin E1 stimulated NG108-15 cells, and by demonstrating very high potency in the mouse vas deferens bioassay. DPE2 binds to the same delta sites as the delta-selective monomer [D-Ala2, D-Leu5] enkephalin, since the two ligands show complete crossdisplacement. Radiolabeled 3H-DPE2 shows a five-fold higher affinity constant, a 2.5-fold higher association rate constant, and a two-fold lower dissociation rate than the monomer. These results are consistent with the hypothesis that the dimeric pentapeptide enkephalin can bridge two delta receptors. This enkephalin dimer provides a valuable new probe of opiate receptors and their organization in cell membranes.
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PMID:Dimeric pentapeptide enkephalin: a novel probe of delta opiate receptors. 629 43

The role of membrane phospholipids in enkephalin receptor-mediated inhibition of adenylate cyclase (EC 4.6.1.1) activity in neuroblastoma X glioma NG108-15 hybrids was studied by selective hydrolysis of lipids with phospholipases. When NG108-15 cells were treated with phospholipase C from Clostridium welchii at 37 degrees C, an enzyme concentration--dependent decrease in adenylate cyclase activity was observed. The basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase activities were more sensitive to phospholipase C (EC 3.1.4.3) treatment than were the NaF-5'-guanylylimidodiphosphate (Gpp(NH)p)-sensitive adenylate cyclase activities. Further, Leu5-enkephalin inhibition of basal or PGE1-stimulated adenylate cyclase activity was attenuated by phospholipase C treatment, characterized by a decrease of enkephalin potency and of maximal inhibitory level. [3H]D-Ala2-Met5-enkephalinamide binding revealed a decrease in receptor affinity with no measurable reduction in number of binding sites after phospholipase C treatment. Although opiate receptor was still under the regulation of guanine nucleotide after phospholipase C treatment, adenylate cyclase activity was more sensitive to the stimulation of Gpp(NH)p. Thus, the reduction of opiate agonist affinity was not due to the uncoupling of opiate receptor from N-component. Further, treatment of NG108-15 hybrid cell membrane with phospholipase C at 24 degrees C produced analogous attenuation of enkephalin potency and efficacy without alteration in receptor binding. The reduction in enkephalin potency could be reversed by treating NG108-15 membrane with phosphatidylcholine, but not with phosphatidylserine, phosphatidylinositol, or cerebroside sulfate. The enkephalin activity in NG108-15 cells was not altered by treating the cells with phospholipase A2 o phospholipase C from Bacillus cereus. Hence, apparently, there was a specific lipid dependency in enkephalin inhibition of adenylate cyclase activity.
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PMID:Attenuation of enkephalin activity in neuroblastoma X glioma NG108-15 hybrid cells by phospholipases. 629 48

The uptake of tritium-labeled [D-Ala2,D-Leu5]enkephalin ([3H]DADLE) by mouse neuroblastoma cells (N4TG1) was investigated under conditions which are optimal for ligand-induced receptor loss (down regulation). Uptake of [3H]DADLE was a receptor-mediated process, since it was inhibited by opiate receptor ligands and the (i) time course, (ii) dose-response curve, and (iii) temperature dependence of uptake were similar to those for enkephalin-receptor down regulation. Cells in suspension showed less uptake than those in monolayer culture and both uptake and down regulation were decreased by the inhibitors of metabolic energy production, sodium azide, and 2,4-dinitrophenol. Comparison of the effects of these metabolic inhibitors on the processes of receptor loss and ligand uptake showed that these cells accumulate [3H]DADLE in excess of their surface receptor number, suggesting that receptor recycling normally occurs under the conditions studied. The lysosomotrophic amines, chloroquine and methylamine, inhibited dissociation of cell-associated [3H]DADLE but did not affect down regulation. The data are consistent with the idea that enkephalin is internalized via receptor-mediated endocytosis. The possible fate of the "down-regulated" receptors is considered.
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PMID:Characterization of the association of tritiated enkephalin with neuroblastoma cells under conditions optimal for receptor down regulation. 629 70

Opiate receptor binding decayed exponentially in mouse neuroblastoma-rat glioma (NG108-15) hybrid cell preparations following exposure to increasing doses of ionizing radiation (0.2 to 7.0 Mrads; 2.0 Mrads/min). Target size analysis revealed that [3H][D-Ala2, D-Leu5]enkephalin (agonist) and [3H]naloxone (antagonist) bound specifically to a component with an apparent molecular size of 200,000 +/- 20,000. Lyophilization of cells for the irradiation procedure did not significantly alter receptor affinity or binding capacity for these ligands. Furthermore, the loss of opiate receptor binding in irradiated cell samples could not be attributed to reduced receptor affinity since increasing concentrations of radiolabeled ligand failed to reverse the inhibition; nonspecific binding decreased only slightly under identical experimental conditions. The value of determining molecular size by radiation inactivation analysis was confirmed by showing that apparent target sizes for two representative lysosomal enzymes (beta-galactosidase and alpha-mannosidase) were consistent with results obtained previously using conventional methods. Thus, the data suggest that the ligand binding component of delta-opiate (enkephalin) receptors in NG108-15 cells has a minimum functional size of approximately 200,000.
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PMID:Molecular size of opiate (enkephalin) receptors in neuroblastoma-glioma hybrid cells as determined by radiation inactivation analysis. 629 28


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