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)

Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybrid cells. In the presence of 7 nM-[3H]Leu-enkephalin, the concentrations at which they caused 50% inhibition of [3H]enkephalin binding (IC50 values) are 0.1 micro M and 0.3 micro M, respectively. In contrast, the synthetic L-Ala2-dermorphin shows very low affinity for the opioid receptors. In addition, like other opioid peptides, dermorphin and hyp6-dermorphin inhibit the elevation by prostaglandin E1 (PGE1) of the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (IC50 values 0.2 micro M and 0.4 micro M, respectively). The inhibition is prevented by the opiate antagonist naloxone, L-Ala2-dermorphin is at least three orders of magnitude less potent in inhibiting the PGE1-evoked increase in the level of cyclic AMP. The results show that peptides with an amino acid sequence quite different from that of the enkephalins can bind to opioid receptors of the hybrid cells.
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PMID:Dermorphins, opioid peptides from amphibian skin, act on opioid receptors of mouse neuroblastoma x rat glioma hybrid cells. 627 80

Partially purified extracts from neuroblastoma X glioma hybrid cells 108CC15 inhibit, like opioids, the prostaglandin E1-evoked formation of cyclic AMP in a dose-dependent manner in the same hybrid cells. The inhibition is prevented by the opioid antagonist naloxone. In addition, the same extract competes with [3H]naloxone and [3H]Leu-enkephalin for binding to opioid receptors of hybrid cell membranes and to a specific antiserum, respectively. The opioid activity in the extracts is destroyed by carboxypeptidase A and leucine aminopeptidase, but not by trypsin. Further purification of the extracts by HPLC, TLC, or high-voltage paper electrophoresis reveals in each case two active fractions which behave like Met- and Leu-enkephalin. The Met-enkephalin-like, but not the Leu-enkephalin-like, fraction is inactivated by treatment with BrCN. Dimethylaminonaphtylsulfonyl (dansyl) derivatives of Met- and Leu-enkephalin correspond to [3H]dansyl derivatives of Met-like substances from hybrid cells. Three to four times as much Met-enkephalin-like as Leu-enkephalin-like material is present in the extract. The overall concentration of opioid peptides in the hybrid cells varies between 0.03 and 1.0 pmol Leu-enkephalin equivalents per mg protein. The amount of opioids in the hybrid cells is strongly dependent on the cell density. The findings suggest that neuroblastoma X glioma hybrid cells contain opioid peptides that are very similar, if not identical, to Met- and Leu-enkephalin. Opioid activity can also be detected in other neuronal cell lines and even in glioma cells.
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PMID:Neuroblastoma X glioma hybrid cells synthesize enkephalin-like opioid peptides. 628 22

The benozomorphan derivative (-)-2-[2-(p-bromoacetamidophenyl)ethyl]-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan (BAB), capable of reacting with nucleophilic groups, acts on neuroblastoma X glioma hybrid cells as a potent, irreversible opiate agonist. Its potency in inhibiting the increase in cellular cyclic AMP, evoked by prostaglandin E1, is comparable to that of Leu-enkephalin. This also applies to its capacity to compete with [3H]D-Ala2-Met-enkephalinamide ([3H]DAEA) in binding on cell membrane preparations. The comparatively lower potency of (-)-2-[2-(p-acetamidophenyl)-ethyl]-5,9 alpha-dimethly-2'-hydroxy-5,7-benzomorphan (AB), which differs from BAB in the substitution of the bromoacetamido group by an acetamido group, is of the same order of magnitude as that of morphine. The covalent interaction of BAB with the opiate receptors is deduced from the observations that (1) it is not possible to wash away this compound from the receptors, (2) the potency of BAB in inhibiting the specific binding of [3H]DAEA increases with prolonged preincubation time, and (3) AB behaves as a reversible agonist.
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PMID:Irreversible activation of the opiate receptor of neuroblastoma X glioma hybrid cells by an alkylating benzomorphan derivative. 631 81

This study reports on the molecular mechanism of delta-opiate receptor down regulation on 108CC15 neuroblastoma X glioma hybrid cells. The down regulation induced by culture in the presence of 10(-5) M 2-D-Ala, 5-D-Leu-enkephalin (DADLE) can be prevented by continued exposure to ligand concentrations greater than 4 nM, the Kd of the binding site. Below this concentration, down regulation is a rapid and irreversible process. It is deduced that the internalization process in this cell line is initiated when unoccupied receptor dimers are present. These results have important implications for down regulation studies using cultured cell lines and studies of receptor regulation in vivo after chronic treatment with neuroactive drugs.
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PMID:Down regulation of opiate receptors on 108CC15 hybrid cells is inhibited by receptor occupancy. 632 48

Human beta-endorphin (beta h-EP) binding on neuroblastoma X glioma hybrid NG108-15 cells using tritiated human beta endorphin (3H-beta h-EP) as a primary ligand was found to have a component which was not displacable with [D-Ser2 )-Leu-enkephalin-Thr6 (DSLET). The beta h-EP binding on these cells after saturation of the delta opiate sites with 200 nM DSLET was further characterized with synthetic beta h-EP analogs. The nonopioid binding site appears to recognize beta h-EP-(6-31), beta h-EP-(21-31) and beta h-EP-(28-31). Under these conditions, these COOH-terminal segments fully displace the tritiated beta h-EP. However, beta h-EP-(1-27) does not further displace 3H-beta h-EP in the presence of DSLET. The fact that a combination of DSLET and beta h-EP-(6-31) results in a full displacement of 3H-beta h-EP provides direct evidence for the existence of two binding sites for beta h-EP in NG108-15 cells, one recognizing the NH2-terminal enkephalin sequence and the other the non-opioid COOH-terminal segment.
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PMID:beta-Endorphin: evidence for the existence of opioid and non-opioid binding components for the tritiated human hormone in NG108-15 cells. 633 52

Human retinoblastoma contains clusters of cells immunoreactive for methionine-enkephalin and methionine-enkephalin-arginine-phenylalanine. Some tumour cells also exhibited methionine-enkephalin-arginine-glycine-leucine-like immunoreactivity. The results are in agreement with those obtained with similar testing of neuroblastoma cell cultures. It is concluded that some human retinoblastoma cells are capable of synthesizing preproenkephalin A or parts of this molecule.
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PMID:Immunohistochemical evidence for preproenkephalin A synthesis in human retinoblastoma. 638 22

Partially purified extracts from neuroblastoma x glioma hybrid cells inhibit via opioid receptors the PGE1-elicited formation of cyclic AMP in the same hybrid cell system. The purification of extracts reveals two active fractions very similar to Met- and Leu-enkephalin by several criteria including treatment with cyanogen bromide. On an average, the intracellular concentration of opioids in hybrid cells is 0.1 pmol per mg protein. The concentration is strongly dependent on the cell density. Furthermore, the content in the hybrids of enkephalin-like peptides is specifically elevated by glucocorticoids.
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PMID:Production and regulation of enkephalin-like peptides in neuroblastoma x glioma cells. 712

Neuroblastoma x glioma hybrid, NG108-15, cells appear to express the alpha-subunit of the guanine nucleotide-binding protein Gs in a substantial molar excess over its effector adenylate cyclase [Kim, Adie and Milligan (1994) Eur. J. Biochem. 219, 135-143]. Addition of the IP prostanoid receptor agonist iloprost to intact NG108-15 cells resulted in a dose-dependent increase in formation of the complex between Gs alpha and adenylate cyclase (GSAC) as measured by specific high-affinity binding of [3H]forskolin. NG108-15 cells transfected to express either relatively high (clone beta N22) or low (clone beta N17) levels of beta 2-adrenoceptor both showed dose-dependent increases in specific [3H]forskolin binding in response to the beta-adrenoceptor agonist isoprenaline, and maximally effective concentrations of isoprenaline resulted in the generation of similar numbers of GSAC complexes in both clones. The dose-effect curve for clone beta N22, however, was some 15-fold to the left of that for clone beta N17, which is similar to that noted for isoprenaline-mediated stimulation of adenylate cyclase activity [Adie and Milligan (1994) Biochem. J. 303, 803-808]. In contrast, dose-effect curves for iloprost stimulation of [3H]forskolin binding were not different in clones beta N22 and beta N17. Basal specific [3H]forskolin binding in the absence of agonist was significantly greater in cells of clone beta N22 than clone beta N17. This was not a reflection of higher immunological levels of adenylate cyclase, indicating that the higher basal formation of GSAC probably reflects empty-receptor activation of Gs. This higher basal specific [3H]forskolin binding was partially reversed by propranolol. The addition of the opioid peptide D-Ala-D-Leu-enkephalin to NG108-15 cells did not reduce iloprost-stimulated [3H]forskolin binding even though this peptide inhibits stimulated adenylate cyclase activity by activation of a delta opioid receptor.
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PMID:Detection and analysis of agonist-induced formation of the complex of the stimulatory guanine nucleotide-binding protein with adenylate cyclase in intact wild-type and beta 2-adrenoceptor-expressing NG108-15 cells. 753 56

The human neuroblastoma cell line SH-SY5Y was used to demonstrate morphine-induced down-regulation and naloxone-induced up-regulation of opiate receptors in a mu receptor containing neuronally derived preparation capable of desensitization to morphine. Chronic exposure to morphine decreased the number but not the affinity of mu opiate receptors in SH-SY5Y cells. Differentiation of the cells with retinoic acid or with the phorbol agent TPA (12-O-tetradecanoyl-phorbol-13-acetate) increased the number of mu receptors. Morphine-induced down-regulation, however, was observed in the absence of differentiation as well as after differentiation with retinoic acid or TPA. The decrease in the number of receptors was related to time of exposure, with a half-maximum disappearance time (T1/2) of about 3 hr during the initial phase. The receptor decrease was near maximum at 24 hr with no further significant change up to 72 hr. The loss of [3H] DAMGO ([3H]Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) binding was also dose-dependent, with reductions occurring at 0.3, 1 and 10 microM. The loss of receptors was dependent on temperature, with reductions at 37 but not 23 degrees C. The down-regulation was blocked by naloxone and the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D(-Trp-)Orn-Thr-Pen-Thr-NH2), but not by the delta antagonist ICI 174864 ([N,N-diallyl-Tyr1,Aib2,3]Leu-enkephalin). Cholinergic ([3H]quinclidinyl benzilate) binding was not affected by the morphine treatment, indicating that the down-regulation was homologous for opiate receptors. In SH-SY5Y cells, unlike other cell models, the opiate antagonist naloxone upregulated mu receptors by more than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mu opiate receptor down-regulation by morphine and up-regulation by naloxone in SH-SY5Y human neuroblastoma cells. 809 44

The effects of activation of the adenylyl cyclase-protein kinase A pathway on the expression of delta-opioid receptor mRNA in the NG108-15 neuroblastoma x glioma cell line has been investigated. Activation of prostaglandin E1 (PGE1) receptors, which are positively coupled to adenylyl cyclase, resulted in a reduction in delta-receptor messenger RNA levels. Direct stimulation of adenylyl cyclase by forskolin or treatment of cells with the cyclic AMP analogue dibutyryl cyclic AMP (db-cAMP) mimicked the effect of PGE1. Down-regulation in receptor protein levels, as measured by loss of radioligand binding sites, was also observed and its extent correlated well with the decrease in the amount of delta-opioid receptor transcripts. D-Ser2-Leu-enkephalin-Thr6 (DSLET) inhibition of adenylyl cyclase activity was also diminished after db-cAMP treatment. Inhibitors of protein kinase A (PKA) partially reversed the PGE1- and db-cAMP-mediated repression of the delta-opioid receptor mRNA levels. The rate of degradation of delta-opioid receptor mRNA in the presence of actinomycin D was not altered in response to db-cAMP, suggesting that mRNA stability is not reduced by PKA action. The regulation of delta-opioid receptor mRNA levels by db-cAMP was not sensitive to the protein synthesis inhibitor cycloheximide, suggesting that de novo protein synthesis is not required in this process.
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PMID:Regulation of delta-opioid receptor mRNA levels by receptor-mediated and direct activation of the adenylyl cyclase-protein kinase A pathway. 900 47


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