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 endogenous central nervous tissue substance called MLC (morphine-like compound) is shown to bind to the opiate receptors of the mouse neuroblastoma X glioma hybrid cell line NG108-15. The interaction of MLC with these opiate receptors is noncooperative, as is the interaction of morphine, naloxone, and Leu-enkephalin with these receptors. A specific antibody to morphine will bind MLC but will not bind beta-endorphin, Leu-enkephalin, or Met-enkephalin. It would appear, therefore, that MLC can be considered to be a different type of endogenous ligand for the opiate receptor.
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PMID:Binding of the endogenous nonpeptide morphine-like compound to opiate receptors. 20 Sep 39

The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
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PMID:Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. 127 91

1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino-1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. 140 9

The endogenous opioids and their receptors are known to play a major role in neoplasia. In the present study, naltrexone (NTX), a potent opioid antagonist, was utilized to explore the interactions of opioids and opioid receptors in mice with transplanted neuroblastoma (S20Y). Tumors from mice subjected to either intermittent (4-6h/day; 0.1 mg/kg NTX) or complete (24 h/day; 10 mg/kg NTX) opioid receptor blockade exhibited an up-regulation of DADLE and Met-enkephalin binding sites, as well as tissue levels of beta-endorphin and Met-enkephalin. Binding affinity to [D-Ala2,D-Leu5]enkephalin (DADLE) or ethylketocyclazocine (EKC), the levels of plasma beta-endorphin, and the anatomical location and quantity of Met- and Leu-enkephalin and cytoskeletal components (i.e. tubulin, actin, brain spectrin (240/235) were similar in NTX and control tumor-bearing animals. Tissue viability of the 0.1 NTX group was increased compared to controls. Both mitotic and labeling indexes were increased during the period of opioid receptor blockade, but decreased in the period subsequent to receptor blockade. NTX treatment produced a 2-fold increased in sensitivity to opioids. Met-enkephalin (10 mg/kg) produced a depression in both mitotic and labeling indexes in tumor-bearing mice that could be reversed by naloxone (10 mg/kg) administration. Thus, the endogenous opioids are trophic agents that inhibit growth by suppressing cell proliferation. The duration of receptor blockade by opioid antagonists modulates these actions, affecting both tumor incidence and survival time. Complete opioid receptor block prevents the interaction of increased levels of putative growth-related peptides with a greater number of opioid receptors, thereby increasing cell proliferation and accelerating tumor growth. With intermittent blockade, an enhanced opioid-receptor interaction occurs during the interval when the opioid antagonist is no longer present, producing an exaggerated inhibitory action on cell proliferation and the repression of tumorigenic events.
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PMID:Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. 254 Aug 73

Regulation of proenkephalin A expression was studied in the human neuroblastoma SK-N-MC cell line with respect to mRNA-level, translation, posttranslational processing of the prohormone and secretion of the processed products into the culture medium. Cells were treated with either norepinephrine (NE), dexamethasone (DEX), dibutyryl-3',5'-cyclic AMP (dbcAMP) or the combination of NE and DEX. In an additional investigation, proenkephalin A mRNA levels were determined after 9 h of treatment with dbcAMP, NE, isoproterenol, NE + propranolol and dbcAMP + DEX. NE or dbcAMP for 1-48 h transiently elevated proenkephalin A mRNA 1.5-4.5 times compared to control. The effect of NE was partially blocked by the beta-adrenoceptor antagonist propranolol and was reproduced by the beta-adrenoceptor agonist isoproterenol, suggesting involvement of the beta-adrenoceptor. DEX alone had no significant effect. However it markedly antagonized the effect of NE but not that of dbcAMP suggesting an action on the beta-adrenoceptor. The intracellular content of Met-enkephalin-Arg6,Phe7 immunoreactivity was increased during drug treatment in parallel with changes in proenkephalin A mRNA. DEX gave no effect. No significant change in the ratio of low versus high molecular weight immunoreactive material could be detected in the cell extracts as determined at different time points. Secretion of immunoreactivity into the culture medium increased 5-fold after 18 h of treatment with NE, whereas dbcAMP gave a 2-fold increase. The proportion of low-molecular weight secreted material increased markedly. DEX alone did not induce any change but inhibited the effect of NE. Apparently, regulation of gene expression, prohormone processing and secretion are coordinated by a cAMP-dependent mechanism.
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PMID:Modulation of proenkephalin A gene expression by cyclic AMP. 254 16

Regulation of preproenkephalin gene expression was studied in NG108-15 neuroblastoma-glioma hybrid cells. Untreated cells contain 20-120 fg preproenkephalin mRNA per microgram cellular RNA. Treatment of cells with a glucocorticoid (e.g. dexamethasone) for 24 hr or 8 days elevated the abundance of this mRNA to 3 or 9 times the control, respectively. Treatment with 8-bromo-cyclic AMP or an adenylate cyclase activator such as prostaglandin E1 or forskolin elevated preproenkephalin mRNA to twice the control or less. Treatment with both glucocorticoid and forskolin for 24 hr or 8 days markedly increased preproenkephalin mRNA to 5-8 and 30 times the control, respectively. Intracellular Met-enkephalin immunoreactivity was increased in parallel with the mRNA abundance. The results demonstrate that preproenkephalin gene expression is synergistically regulated by glucocorticoids and cAMP.
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PMID:Glucocorticoids and cyclic AMP synergistically regulate the abundance of preproenkephalin messenger RNA in neuroblastoma-glioma hybrid cells. 302 Nov 19

Several human tumour cell lines were screened for secretion of proenkephalin-derived peptides with an antiserum directed to its N-terminus, Met-enkephalin-Arg6,Phe7 and for proopiomelanocortin-derived peptides with an antiserum to beta-endorphin. The neuroblastoma SK-N-MC cell line secreted Met-enkephalin-Arg6,Phe7-immunoreactive peptides in relatively high amounts into the culture medium, although processing was not complete and there was no evidence for free Met-enkephalin-Arg6,Phe7. Gene expression was confirmed by the presence of proenkephalin mRNA and proenkephalin-derived polypeptides in extracts of the SK-N-MC cells and also in the neuroblastoma SH-SY5Y cell line. In the latter cells, however, the expression was approximately 3 times lower, there was less processing of proenkephalin and no evidence for secretion.
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PMID:Expression of the proenkephalin gene in human neuroblastoma cell lines. 338 40

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

Mouse neuroblastoma Neuro-2a cells were examined for the expression of pro-enkephalin mRNA, protein, and Met-enkephalin ([Met]-Enk) peptide. Reverse transcriptase/polymerase chain reaction (RT/PCR) and in situ hybridization demonstrated the presence of pro-enkephalin mRNA in these cells. Immunocytochemistry using an antibody which recognizes pro-enkephalin and high pressure liquid chromatography (HPLC) followed by radioimmunoassay indicated that pro-enkephalin was synthesized in these cells and processed to yield the bioactive pentapeptide, [Met]-Enk. Furthermore, release studies showed that the [Met]-Enk was secreted from these cells with high K+ stimulation. Using double labeling, in situ hybridization combined with immunocytochemistry, we demonstrated that prohormone convertase 2 (PC2) mRNA is colocalized with pro-enkephalin in the same Neuro-2a cells, suggesting that this enzyme may be responsible for processing this precursor. we also showed the presence of vasopressin mRNA and arginine-vasopressin peptide in these cells using in situ hybridization and immunocytochemistry, respectively. Thus, the Neuro-2a cells are a multiple neuropeptide-producing cell line and an excellent model for studying the mechanisms involved in the synthesis, intracellular targeting and processing of endogenous pro-enkephalin and pro-vasopressin, as well as other transfected neuropeptide precursors.
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PMID:The Neuro-2a neuroblastoma cell line expresses [Met]-enkephalin and vasopressin mRNA and peptide. 867 23

Down-regulation of opiate receptors is demonstrated more easily in vitro than in vivo. The possible role of endogenous opiate-modulating peptides in preventing such down-regulation was investigated by addition of Tyr-W-MIF-1 to an in vitro preparation, the human neuroblastoma cell line SH-SY5Y, in which down-regulation of opiate receptors has been demonstrated previously. Although both morphine and Met-enkephalin down-regulated mu and delta receptors after chronic (24 h) exposure in serum-free medium, Tyr-W-MIF-1, at doses of up to 100 microM, did not affect receptor number when administered alone. This lack of effect could not be attributed to degradation of the peptide during chronic treatment because high-performance liquid chromatography showed that 79% of the peptide remained intact after a 24-h incubation. When coadministered with 3 microM morphine, Tyr-W-MIF-1 dose-dependently attenuated morphine-induced down-regulation of both mu and delta receptors. Down-regulation of mu receptors by the selective agonist PL017 was also attenuated by Tyr-W-MIF-1, but down-regulation of delta receptors by the selective agonist DPDPE was not. These studies indicate that endogenous opiate modulators may play a role in opiate tolerance at the level of receptor down-regulation.
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PMID:Tyr-W-MIF-1 attenuates down-regulation of opiate receptors in SH-SY5Y human neuroblastoma cells. 945 5


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