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)

Inositol uptake was studied in the rat CNS neuroblastoma B50 cell line. Eadie-Hofstee analysis of the uptake pattern reveals two defined modes of inositol entry into the cell. The high-affinity uptake component requires the presence of extracellular sodium and is inhibited by phloridzin. Analysis of the uptake velocities of the high-affinity uptake component provided the following apparent kinetic parameters: Km = 13.7 microM and Vmax = 14.7 pmol/mg of protein/min (without correcting for residual diffusion) and Km = 12.9 microM and Vmax = 12.3 pmol/mg of protein/min (with correction). At physiological concentrations, the high-affinity transport process contributes approximately 70% to total uptake; the remainder is due to a low-affinity diffusion-like process. Uptake inhibition studies reveal that the uptake process is sensitive to ouabain, amiloride, and dichlorobenzamil inhibition but relatively insensitive to cytochalasin B or phloretin. When neuroblastoma B50 cells are induced to differentiate morphologically with high extracellular calcium or with dibutyryl cyclic AMP, a significant decrease in inositol uptake is observed. The dibutyryl cyclic AMP-mediated inhibition of uptake affects only the high-affinity uptake component and is noncompetitive in nature. The high extracellular calcium-mediated inhibition is less specific; it involves "disappearance" of the high-affinity process, some inhibition of the low-affinity process, and an increase of inositol efflux. The significance of these observations is discussed in the context of neuroblastoma B50 cell differentiation.
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PMID:Inositol metabolism during neuroblastoma B50 cell differentiation: effects of differentiating agents on inositol uptake. 216 74

Three distinct antipeptide antisera generated against synthetic peptides that represent parts of the primary sequence of the alpha-subunit of the (pertussis toxin-sensitive) guanine nucleotide binding protein G0 were used in two-dimensional immunoblots of membranes of neuroblastoma X glioma (NG108-15) cells. Each antiserum identified two distinct polypeptides of some 39 kDa. These had apparent isoelectric points of 5.5 and 5.8. Differentiation of NG108-15 cells in response separately to dibutyryl cyclic AMP (cAMP), 8-bromo cAMP, forskolin, and prostaglandin E1 produced elevated levels of G0 alpha, as has previously been noted in one-dimensional immunoblots. Two-dimensional analysis demonstrated that the cAMP-induced increases in levels of G0 alpha were only of the more acidic isoform. The two isoforms were both substrates for pertussis toxin-catalysed ADP-ribosylation and did not appear to represent differentially phosphorylated forms of the same polypeptide. Separation of the two forms of G0 alpha could be achieved in one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis when 4 M deionized urea was included in the resolving gel. The more slowly migrating band was the acidic form and corresponded exactly in mobility with the major form of G0 from both rat and mouse brain. There was no equivalent in brain of the more rapidly migrating form of G0 from the cells. In agreement with the data from two-dimensional gels, only the more slowly migrating form was expressed in considerably higher amounts following cAMP-induced differentiation of NG108-15 cells. Of these two forms of "G0," the acidic species is equivalent to G0 from brain, but the basic form is not identical with G0*, which has been purified from bovine brain.
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PMID:Identification of two distinct isoforms of the guanine nucleotide binding protein G0 in neuroblastoma X glioma hybrid cells: independent regulation during cyclic AMP-induced differentiation. 217 64

We investigated the ability of two forms of Pituitary Adenylate Cyclase Activating Polypeptide [PACAP-38, the 38 amino acid peptide isolated from ovine hypothalamus, and PACAP-27, a shorter N-terminal (1-27) amidated version] to interact with specific receptors in membranes from the human neuroblastoma cell line NB-OK. [125I]PACAP-27 bound rapidly and specifically to one class of high affinity sites (Kd 0.5 nM). VIP inhibited [125I]PACAP-27 binding 300- to 1000-fold less potently than PACAP-27 and PACAP-38. One microM PHI prevented tracer binding only partially and secretin, glucagon and GRF(1-29)NH2 were ineffective in this respect. PACAP-27 and PACAP-38 stimulated adenylate cyclase activity dose dependently and with similar efficacy (Kact 0.2-0.3 nM), this activation being compatible with the occupancy of specific high affinity PACAP receptor. VIP was markedly less potent and less efficient on this enzyme than PACAP. Chemical cross-linking of [125I]PACAP-27 followed by SDS-PAGE and autoradiography revealed specific cross-linking with a 68 kDa protein.
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PMID:The novel VIP-like hypothalamic polypeptide PACAP interacts with high affinity receptors in the human neuroblastoma cell line NB-OK. 217 43

The effects of the neurotoxin aluminum on markers of synaptic neurotransmission, adenosine 3',5'-monophosphate, and neurofilaments have been evaluated in a neuroblastoma x glioma hybridoma (NG108-15). Cells were exposed for 4 days to 2 mM aluminum lactate, a concentration that did not suppress growth. Compared to controls, the activity of choline acetyltransferase was significantly increased by 37% associated with an up-regulation in enzyme activity (Vmax). Muscarinic receptors, measured by [3H]QNB binding, were reduced by 41%. In contrast, the activities of acetylcholinesterase and glutamate decarboxylase were not significantly changed. Aluminum raised the level of cyclic AMP by 20%, although adenylate cyclase activity was unchanged. Small amounts of both phosphorylated and non-phosphorylated neurofilaments were detected in NG108-15 cells. Aluminum intoxication, however, did not alter the quantity, ultrastructure, or immunoreactivity of neurofilaments. Our results demonstrate the capability of aluminum to produce selected changes in cholinergic markers and levels of cyclic AMP in a rapidly dividing cell line.
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PMID:The effect of aluminum on markers for synaptic neurotransmission, cyclic AMP, and neurofilaments in a neuroblastoma x glioma hybridoma (NG108-15). 217 66

1. Using [3H]DHA and unlabeled L-alprenolol, a substantial amount of over 64% specific binding of beta-adrenergic receptor has been identified on the neuroblastoma x glioma hybrid NG108-15 cell, which has been proven to display numerous functional characteristics of intact neurons. 2. Beta-adrenergic receptor binding on intact NG108-15 cells does not change significantly upon morphological differentiation, induced by 1 mM dibutyryl cyclic AMP (dBcAMP). 3. The [3H]DHA binding on intact NG108-15 cells is rapid, saturable, and reversible, having a t1/2 of 1.0 min for association and 3.5 min for dissociation. 4. The affinity constant (Kd) and maximum binding capacity (Bmax) for binding of [3H]DHA to beta-adrenergic receptors on NG108-15 cells have been estimated by Scatchard plot analysis to be 2.5 and 0.23 nM, respectively. Further analysis indicates a single class of receptors for [3HDHA binding on NG108-15 cells. 5. Studies on kinetic properties have revealed on-rate (K + 1) and off-rate (K - 1) constants of 0.7 X 10(-9) M min-1 and 0.19 min-1, respectively. Further, the IC50 value and inhibition constant (Ki) for unlabeled L-alprenolol to inhibit [3HDHA binding on NG108-15 cells have been estimated to be 10(-5) and 8.9 X 10(-6) M, respectively. 6. The rank-order potency of catecholamine agonists, (-)ISO greater than (+)ISO greater than EPI greater than NE, reveals the presence of type 2 receptor for the beta-adrenergic binding on both differentiated and undifferentiated NG108-15 cells. 7. The present study indicates that the clonal neuroblastoma x glioma hybrid NG108-15 cell line possesses substantial amounts of beta-adrenergic receptors with characteristics similar to those on neuronal cells.
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PMID:Identification and characterization of the beta-adrenergic receptor on neuroblastoma x glioma hybrid NG108-15 cells. 217 41

Mouse neuroblastoma x rat glioma hybrid NG108-15 cells form cholinergic synapses with rat or mouse muscle cells in culture. The rate of synapse formation is greatly dependent on intracellular cyclic AMP concentrations. The synapse formation is lower in the presence of glia maturation factor, a partially purified brain extract. Once the synapse between NG108-15 cells and myotubes has been formed, this synapse is stable for days. Extracellular application of serotonin, PGF2 alpha, PGD2, neurotensin and bradykinin on NG108-15 cells increases synaptic transmission. Since bradykinin increases the level of intracellular inositol 1,4,5-trisphosphate (InsP3), bradykinin-induced facilitation is due to InsP3-dependent elevation of intracellular Ca concentrations.
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PMID:Cholinergic synapse formation between NG108-15 and muscle cells and modulation of transmission. 217 13

The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), which causes differentiation of SH-SY5Y neuroblastoma cells, reduces carbachol binding and carbachol-stimulated Ca2+ mobilization in these cells. The decrease in responsiveness to carbachol is due partially to a reduction in the amount of Ca2+ released by the cells and partially to a decrease in the sensitivity of the cells to carbachol. These effects probably can be attributed to a reduction in muscarinic receptor number and a decrease in receptor affinity, respectively. Forskolin, an alkaloid known to cause an increase in cellular cyclic AMP, enhances Ca2+ influx into the cells without affecting the cytosolic free Ca2+ concentration. The alkaloid causes an apparent restoration of the reduced Ca2+ release, caused by TPA, but does not affect the sensitivity of the cells to carbachol. Forskolin increases the decay of carbachol-induced increase in cytosolic Ca2+. The effects of TPA appear to be linked directly to receptor function, whereas those of forskolin are due to the effect of cyclic AMP on cellular Ca2+ metabolism.
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PMID:12-O-tetradecanoylphorbol 13-acetate and forskolin modify muscarinic receptor-linked Ca2+ mobilization in SH-SY5Y neuroblastoma cells through different mechanisms. 229 48

Voltage-gated sodium currents and acetylcholine-elicited currents in clonal rat pheochromocytoma cells (PC12) were studied using the whole-cell patch-clamp technique. After treatment of cultures with nerve growth factor (NGF, 2-4 nM) for 5 or more days, both Na currents and ACh responses increased by 5-7-fold. We tested the ability of a number of treatments reported to induce physiological differentiation in neuroblastoma or neuroblastoma-glioma hybrid cells. We found that no treatment was as effective as NGF, and mitotic inhibitors and 8-bromocyclic AMP reduced the efficacy of NGF at increasing both sodium currents and ACh responses. Some treatments were able to selectively reduce or enhance the ability of NGF to induce ACh responses or sodium currents. Dexamethasone, in particular, completely blocked the NGF-induced increase in ACh response, while leaving Na currents unaffected. Furthermore, in individual cells the Na current density and ACh current density are uncorrelated. These observations indicate that physiological differentiation in PC12 cells is regulated differently than in neuroblastoma cells and, further, in PC12 cells sodium currents and ACh responses are independently regulated.
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PMID:Regulation of sodium currents and acetylcholine responses in PC12 cells. 230 64

Sodium and calcium inward currents (INa and ICa) were measured in neuroblastoma X glioma hybrid cells of clones 108CC5 and 108CC15 by a single suction pipette method for internal perfusion and voltage clamp. Morphologically undifferentiated, exponentially growing cells were compared with cells differentiated by cultivation with 1 mmol/l dibutyryl cyclic AMP. Outward currents were eliminated by perfusing the cells with a K+-free solution. Voltage dependence and ion selectivity as well as steady state inactivation characteristics of INa and ICa resembled those of differentiated mouse neuroblastoma cells, clone N1E-115 (Moolenaar and Spector 1978, 1979). These parameters were identical in undifferentiated and differentiated cells of both clones. After differentiation the average density of the peak sodium and calcium currents was increased two and four-fold, respectively, in both cell lines. Our data indicate that exponentially growing, morphologically undifferentiated 108CC5 and 108CC15 neuroblastoma X glioma hybrid cells possess functional Na+ and Ca2+ channels undistinguishable from those of non-proliferating cells of these clones differentiated morphologically by treatment with dibutyryl cyclic AMP. That Na+ and Ca2+ spikes were not detected by other authors in these cells prior to morphological differentiation by dibutyryl cyclic AMP may be attributed to the fact that at the low resting membrane potential measured the Na+ and Ca2+ channels are inactivated.
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PMID:Sodium and calcium currents in neuroblastoma x glioma hybrid cells before and after morphological differentiation by dibutyryl cyclic AMP. 241 25

The kinetics of activation and inactivation of the inward calcium current (ICa) in morphologically undifferentiated and differentiated neuroblastoma X glioma hybrid cells of the clone 108CC15 were studied by the suction pipette technique for internal perfusion and voltage clamping. Potassium currents were eliminated by internal perfusion of the cells with a K+-free solution. Activation of ICa followed a sigmoidal time course and could reasonably be fitted by a m2 relation. The kinetics of ICa inactivation were studied by analyzing the current inactivation during long depolarizing steps and by measuring the peak ICa as a function of the length of a prepulse. Both methods gave comparable results indicating that the ICa inactivation cannot be fitted by a single exponential. The ICa inactivation was fitted by a biexponential function. Neither the activation nor the inactivation of ICa were changed after morphological cell differentiation induced by treatment with dibutyryl cyclic AMP.
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PMID:A kinetic analysis of the inward calcium current in 108CC15 neuroblastoma x glioma hybrid cells. 241 26


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