UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of binding sites have previously been described for neuropeptide Y (NPY), called Y1 and Y2 receptors. The intracellular events following Y1 receptor activation was studied in the human neuroblastoma cell line SK-N-MC. Both NPY and the specific Y1 receptor ligand, [Leu31,Pro34]-NPY, caused a rapid and transient increase in the concentration of free calcium in the cytoplasm as measured by the fluorescent probe, Fura-2. The effect of both peptides was independent of extracellular calcium as addition of EGTA or manganese neither changed the size nor the shape of the calcium response. The calcium response to NPY was abolished by pretreatment with thapsigargin, which can selectively deplete a calcium store in the endoplasmic reticulum. Y1 receptor stimulation, by both NPY and [Leu31,Pro34]NPY, also inhibited the forskolin-stimulated cAMP production with an EC50 of 3.5 nM. There was a close relation between the receptor binding and the cellular effects as half-maximal displacement of [125I-Tyr36]monoiodoNPY from the receptor was obtained with 2.1 nM NPY. The Y2-specific ligand NPY(16-36)peptide had no effect on either intracellular calcium or cAMP levels in the SK-N-MC cells. It is concluded that Y1 receptor stimulation is associated with both mobilization of intracellular calcium and inhibition of adenylate cyclase activity.
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PMID:Y1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase. 215 77

Dopamine stimulated human neuroblastoma SK-N-MC cells to accumulated cyclic AMP. The D1 agonist SKF (R)-38393 also stimulated cyclic AMP production whereas the response to dopamine was inhibited by the D1 antagonist SCH (R)-23390. Membranes from SK-N-MC cells bound the D1 ligand [125I]SCH 23982 with a Kd of 2.1 nM and a Bmax of 102 fmol/mg protein. Binding was displaced by dopamine, SKF 38393, and SCH 23390. Up to 40% of the receptors were in an agonist high affinity, guanine nucleotide-sensitive state, compared to only 6% in rat striatum. A D1 photoaffinity probe labeled a 72 kDa protein in both SK-N-MC and rat striatal membranes. Thus, SK-N-MC human neuroblastoma cells contain D1 dopamine receptors which are similar to those found in mammalian striatum, but which are more tightly coupled to adenylate cyclase. SK-N-MC cells may be a useful model to investigate the properties and regulation of D1 dopamine receptors.
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PMID:Identification and characterization of functional D1 dopamine receptors in a human neuroblastoma cell line. 215 12

Many cells develop an adaptive increase in the capacity of adenylate cyclase to synthesize cyclic AMP (cAMP) after prolonged (hours or days) exposure to drugs which initially inhibit enzyme activity. Recent evidence suggests that adaptive increases in cAMP responses can be induced within minutes by inhibitory drugs. We have investigated the kinetics for induction and decay of this phenomenon in mouse neuroblastoma x rat glioma hybrid cells. The muscarinic cholinergic agonist carbachol induced an increase in prostaglandin E1-stimulated cAMP accumulation within 2 min of pretreatment with carbachol; the increase was 70 to 100% above control values after exposure to carbachol for 30 min. Enhanced cAMP responsiveness decayed with a half-life of about 8 min after removal of carbachol. Pretreatment with carbachol for 30 hr led to an enhanced cAMP response which decayed in two components, a rapid component and an additional, more stable component which persisted for at least 2 hr after withdrawal of carbachol. Pertussis toxin prevented these effects of carbachol. Prevention of carbachol-induced inhibition of cAMP accumulation below basal concentrations with a phosphodiesterase inhibitor did not prevent the ability of carbachol to acutely induce augmented prostaglandin E1-stimulated cAMP accumulation. Mouse neuroblastoma x rat glioma hybrid cells exhibit an enhanced cAMP response after both acute and chronic exposure to a muscarinic cholinergic agonist although these processes decay with different time courses. The signal for this acutely induced adaptation does not appear to be the decrease in cellular cAMP concentration resulting from inhibition of adenylate cyclase but does require a pertussis toxin-sensitive substrate.
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PMID:Activation of muscarinic cholinergic receptors in mouse neuroblastoma x rat glioma hybrid cells: rapid induction of enhanced capacity of prostaglandin E1 receptors to stimulate cyclic AMP accumulation. 215 56

Treatment of NG108-15 neuroblastoma x glioma cells (24 h) with cholera toxin (0.1-10 micrograms/ml) resulted in a concentration-dependent reduction of the membrane levels of subunits of GTP-binding regulatory proteins (G proteins), as determined by quantitative immunoblot procedures. The extent of reduction differed for different types of subunits: the levels of Go alpha and G beta 1 were reduced by 40-50%, whereas those of G alpha common immunoreactivity and Gi2 alpha were only reduced by 10-20% following treatment with 10 micrograms/ml cholera toxin. This effect of the toxin could not be mimicked by incubation with the resolved B oligomer of cholera toxin, nor by exposure of cells to agents able to raise the intracellular levels of cAMP. Basal adenylate cyclase was stimulated in a biphasic manner by cholera toxin, being stimulated at low concentrations (0.01-10 ng/ml) and then decreased at high (0.1-10 micrograms/ml) concentrations. Thus, the down regulation of G-protein subunits produced by cholera toxin requires its (ADP-ribosyl)transferase activity but does not result from a cAMP-mediated mechanism. The toxin-mediated decrease of Go alpha in the membrane was correlated with a diminution of opioid-receptor-mediated stimulation of high-affinity GTPase activity, suggesting that opioid receptors interact with Go in native membranes of NG108-15 cells. Northern-blot analysis of cytoplasmic RNA prepared from cells treated with cholera toxin showed that the levels of mRNA coding for G beta 1 did not change. Thus, the cholera-toxin-induced decrease of G-protein subunits may not result from an alteration in mRNA levels, but may involve a direct effect of the toxin on the process of insertion and/or clearance of G proteins into and/or from the membrane. These data indicate that cholera toxin, besides catalyzing the ADP-ribosylation of Gs and Gi/Go types of G proteins, can also reduce the steady state levels of Go alpha and G beta 1 subunits in the membrane and thus alter by an additional mechanism the function of inhibitory receptor systems.
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PMID:Cholera toxin differentially decreases membrane levels of alpha and beta subunits of G proteins in NG108-15 cells. 215 84

Mouse neuroblastoma x rat glioma hybrid cells (NG108-15) express an opioid receptor of the delta subclass which both stimulates high-affinity GTPase activity and inhibits adenylate cyclase by interacting with a pertussis-toxin-sensitive guanine-nucleotide-binding protein(s) (G-protein). Four such G-proteins have now been identified without photoreceptor-containing tissues. We have generated anti-peptide antisera against synthetic peptides which correspond to the C-terminal decapeptides of the alpha-subunit of each of these G-proteins and also to the stimulatory G-protein of the adenylate cyclase cascade (Gs). Using these antisera, we demonstrate the expression of three pertussis-toxin-sensitive G-proteins in these cells, which correspond to the products of the Gi2, Gi3 and Go genes, as well as Gs. Gi1, however, is not expressed in detectable amounts. IgG fractions from each of these antisera and from normal rabbit serum were used to attempt to interfere with the interaction of the opioid receptor with the G-protein system by assessing ligand stimulation of high-affinity GTPase activity, inhibition of adenylate cyclase activity and conversion of the receptor to a state which displays reduced affinity for agonists. The IgG fraction from the antiserum (AS7) which specifically identifies Gi2 in these cells attenuated the effects of the opioid receptor. This effect was complete and was not mimicked by any of the other antisera. We conclude that the delta-opioid receptor of these cells interacts directly and specifically with Gi2 to cause inhibition of adenylate cyclase, and that Gi2 represents the true Gi of the adenylate cyclase cascade. The ability to measure alterations in agonist affinity for receptors following the use of specific antisera against a range of G-proteins implies that such techniques should be applicable to investigations of the molecular identity of the G-protein(s) which interacts with any receptor.
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PMID:Delta-opioid-receptor-mediated inhibition of adenylate cyclase is transduced specifically by the guanine-nucleotide-binding protein Gi2. 215 80

Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a covalently bound form. Although there are some discrepancies in the molecular weights of these proteins, it is significant that many investigators have reported a molecular weight of about 60 kd for the receptor, regardless of whether it is of the mu, delta, or kappa type. This finding, together with immunological evidence, suggests that different opioid receptor types may be highly similar, and could conceivably even share a common ligand-binding subunit. Several groups have prepared monoclonal or polyclonal antibodies to purified opioid-binding proteins, which should be useful in mapping the brain regional distribution of the opioid receptors, determining the regions in the peptide involved in ligand binding and association with second messengers, and in determining the relationships among different opioid receptor types. One group has in fact already established an antigenic similarity between a mu-selective opioid-binding protein in mammalian brain, and the delta opioid receptor in NG108-15 neuroblastoma-glioma hybrid cells. One group has reported cloning of the cDNA for a purified opioid-binding protein. Somewhat surprisingly, its predicted amino acid sequence places it in the immunoglobulin superfamily, with strongest homologies to cell-adhesion molecules such as N-CAM. MAG, amalgam and fasciclin II, as well as receptors for peptides such as PDGF and interleukin-6. However, this is consistent with evidence that opioids can modulate cell-cell interactions of monocytes, and provides further support for links between opioids and the immune system. The second messengers mediating opioid actions are still unknown. Opioid agonists affect the activity of adenylate cyclase and ion channels in some tissues, but neither has been shown to mediate opioid analgesia. The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers.
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PMID:Molecular characterization of opioid receptors. 216 Jul 90

We have examined the effects of increasing membrane polyunsaturated fatty acids (PUFAs) on adenosine receptor function in intact N1E-115 neuroblastoma cells. Addition of linoleic acid to the culture medium for 48 h resulted in an approximate threefold increase in the amount of omega 6 fatty acids esterified to membrane phospholipids. Basal cAMP accumulation was significantly higher in the PUFA-enriched cells than in controls, although the differences could be diminished by approximately 75% by treatment of the cells with adenosine deaminase or 8-phenyltheophylline. Exposure of the cultures to the stable adenosine analogue 5'-N-ethylcarboxyamide adenosine (NECA) resulted in concentration-dependent increases in cAMP accumulation. Data from saturation experiments indicated that the maximum amount of cAMP that could be formed in response to NECA in the PUFA-enriched cells was twice that in control cells. Also, the amount of agonist required to elicit half maximal stimulation in the supplemented cells was significantly less than in the control cells (mean values for EC50, 0.85 and 1.43 microM, respectively). The results of this study demonstrate that membrane PUFA have the ability to modify interactions between adenosine receptors and adenylate cyclase in neural cells, a fact that is of potential importance in considering the central role that adenosine plays as a neuromodulator in the nervous system.
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PMID:Effects of membrane polyunsaturated fatty acids on adenosine receptor function in intact N1E-115 neuroblastoma cells. 216 75

We identified receptors for neuropeptide Y (NPY) on an established human neuroblastoma cell line, SK-N-MC, which are functionally coupled to adenylate cyclase through the inhibitory guanine nucleotide-binding protein of adenylate cyclase, Gi. Intact SK-N-MC cells bound radiolabeled NPY with a KD of 2 nM and contained approximately 83,000 receptors/cell. Unlabeled porcine and human NPY and structurally related porcine peptide YY (PYY) competed with labeled NPY for binding to the receptors. NPY inhibited cyclic AMP accumulation in SK-N-MC cells stimulated by isoproterenol, dopamine, vasoactive intestinal peptide, cholera toxin, and forskolin. NPY inhibited isoproterenol-stimulated cyclic AMP production in a dose-dependent manner, with half-maximal inhibition at 0.5 nM NPY. Porcine and human NPY and porcine PYY gave similar dose-response curves. NPY also inhibited basal and isoproterenol-stimulated adenylate cyclase activity in disrupted cells. Pertussis toxin treatment of the cells completely blocked the ability of NPY to inhibit cyclic AMP production and adenylate cyclase activity. The toxin catalyzed the ADP-ribosylation of a 41-kDa protein in SK-N-MC cells that corresponds to Gi. The receptors on SK-N-MC cells appeared to be specific for NPY, as other neurotransmitter drugs, such as alpha-adrenergic, dopaminergic, muscarinic, and serotonergic antagonists, did not compete for either NPY binding or NPY inhibition of adenylate cyclase. Thus, SK-N-MC cells may be a useful model for investigating NPY receptors and NPY-mediated signal transduction.
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PMID:Characterization of functional neuropeptide Y receptors in a human neuroblastoma cell line. 216 71

Treatment of neuroblastoma x glioma hybrid, NG108-15, cells with prostaglandin E1, which in these cells activates adenylate cyclase, produced a marked (50%) reduction in immunologically detectable levels of Gs alpha associated with the plasma membrane. This effect was dependent both on the time of treatment and on the concentration of the receptor ligand used and did not involve a translocation of Gs alpha from the membrane to the cytoplasm of the cells. Both the 45- and 42-kDa forms of Gs alpha which are expressed by these cells were reduced in levels by treatment with the agonist but the greater effect was on the more prevalent 45-kDa polypeptide. By contrast, treatment of the cells with forskolin over the same period did not produce a reduction in levels of Gs alpha, indicating that the effect of prostaglandin E1 was independent of cAMP production. Prostaglandin E1-mediated down-regulation of Gs alpha levels was not produced at the transcriptional level as amounts of mRNA encoding Gs alpha were not reduced by treatment of the cells with agonist. Further, treatment of NG108-15 cells with cycloheximide, throughout the time period required to produce maximal prostaglandin E1-dependent down-regulation of Gs alpha, demonstrated that complete suppression of de novo protein synthesis could not mimic the effect of prostaglandin E1 and hence even complete inhibition of transcription of the Gs alpha gene and/or translation of pre-existing mRNA could not account for these results. Prostaglandin E1 treatment of the cells had no effect on steady-state levels of the alpha subunits of the pertussis toxin-sensitive G-proteins, Gi2, Gi3, Go, which are expressed by these cells or on the level of G-protein beta subunit. Fluoride stimulation of adenylate cyclase activity in membranes of S49 cyc- cells following addition of sodium cholate extracts of membranes of prostaglandin E1-treated NG108-15 cells was only some 50% as effective as with equivalent extracts from untreated cells. These results provide evidence for a novel mechanism of receptor-mediated control of the stimulation of adenylate cyclase, involving reduction in the steady-state amounts of Gs alpha.
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PMID:Prostaglandin E1-mediated, cyclic AMP-independent, down-regulation of Gs alpha in neuroblastoma x glioma hybrid cells. 217 Mar 66

Secretin receptors in membranes from the neuroblastoma-glioma hybrid cell line NG108-15 were investigated by 125I-secretin binding and adenylate cyclase activation. On both parameters the corresponding relative potencies of parent peptides were, respectively: secretin greater than helodermin greater than peptide histidine isoleucinamide = vasoactive intestinal peptide. With secretin analogs and secretin fragments, the order of potency for binding was: secretin = [Val5]secretin greater than [Ala2]secretin = [Ala11]secretin greater than [Ala4, Val5] secretin greater than [Ala4]secretin greater than [D-Phe4] secretin greater than [D-Phe2]secretin = secretin (2-27) greater than secretin (3-27) greater than secretin (7-27). Also, on adenylate cyclase, [D-Phe4]secretin, [D-Phe2]secretin, secretin (2-27) and secretin (3-27) were partial agonists while secretin (7-27) was ineffective. The differentiating agent N6,2'-O-dibutyryladenosine 3',5'-monophosphate (1 mM) increased the density of secretin receptors and secretin-stimulated adenylate cyclase activity after a lag period of 4 h. After incubation for 24 h, receptor number and enzyme activity were increased 4- and 3-fold, respectively. These effects were inhibited totally by 1 microgram/ml cycloheximide and halved by 5 micrograms/ml actinomycin D. They were mimicked by 1 mM sodium butyrate but were not reproduced by either 8-bromoadenosine 3',5'-monophosphate or the phosphodiesterase inhibitor rac-4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone.
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PMID:Secretin receptors in the neuroglioma hybrid cell line NG108-15. Characterization and regulation of their expression. 217 30

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