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)

Receptor-mediated formation of inositol 1,4,5-trisphosphate (IP3) can induce an outward Ca(2+)-activated K+ current [IK(Ca)] in some neural cells. We have investigated IK(Ca) activated by intracellular injections of IP3 in whole-cell patch-clamped neuroblastoma x glioma hybrid cells. The current could only be recorded reliably using citrate as the anion in the pipette, but not using acetate, aspartate, chloride, fluoride, gluconate or methylsulphate. This could be attributed to buffering of intracellular Mg2+ by citrate. Theoretical calculations suggested free [Mg2+] of 1.0 and 0.07 mM respectively in the acetate- and citrate-based recording solutions. Further, IP3-activated IK(Ca) could be recorded when the free Mg2+ level in the acetate, chloride or methylsulphate solutions was lowered to the range (0.05 mM) calculated for the citrate solution. Thus, raised [Mg2+] blocks IK(Ca). This appeared to be due to inhibition of the response to released Ca2+, since high [Mg2+] also blocked the response to intracellular injections of Ca2+ ions. Mean Mg2+ levels in intact neuroblastoma x glioma hybrid cells measured by Mag-Indo-1/AM fluorescence were estimated to be less than 0.14 mM. We therefore conclude that IP3-induced IK(Ca) is expressed under normal conditions, but may be subject to regulation by intracellular Mg2+.
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PMID:Intracellular Mg2+ inhibits the IP3-activated IK(Ca) in NG108-15 cells. [Why intracellular citrate can be useful for recording IK(Ca)]. 159 89

SK-N-SH neuroblastoma cells grown under standard culture conditions contain significant amounts of Mead acid (20:3 omega 9) in phospholipids, indicating essential fatty acid (EFA) deficiency. The amount of esterified 20:3 omega 9 was augmented by growth in a chemically defined EFA-free medium, whereas its presence could be virtually eliminated by supplementation of the culture medium with either arachidonic (20:4 omega 6; AA), eicosapentaenoic (20:5 omega 3; EPA), or linolenic (18:3 omega 3) acids. Substitution of Mead acid for omega 6 fatty acids, particularly evident in phosphatidylinositol (PI), indicates a compensatory replacement of omega 9 for omega 6 fatty acids during EFA deficiency. Studies evaluating [3H]scopolamine binding to the M3 muscarinic acetylcholine receptors (mAChRs) present in these neurotumor cells as well as effects of carbachol on phosphoinositide turnover and intracellular Ca2+ mobilization, indicate that the biosubstitution of 20:4 omega 6 with 20:3 omega 9 does not detectably impair these measures of signal transduction. Stimulation of mAChRs with carbachol increased the cellular mass of diacylglycerol (DAG) approximately 60%. On the basis of distinctive fatty acid "signatures" of each of the phospholipid classes, it is concluded that the DAG initially released following muscarinic stimulation is derived from phosphoinositide breakdown. After several minutes, however, a significant amount of DAG comes from phosphatidylcholine (PC) as well. In contrast to DAG, the composition of phosphatidate (PA) following receptor stimulation closely resembles that of the phosphoinositides, even at the later time points examined. These results support a selective phosphorylation of DAG arising from the stimulated breakdown of phosphoinositides, favoring the conservation of the 1-stearoyl, 2-arachidonoyl (or 20:3 omega 9) moiety.
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PMID:Essential fatty acid deficiency in cultured SK-N-SH human neuroblastoma cells. 163 88

The addition of bradykinin to populations of fura-2 loaded N1E-115 neuroblastoma cells produced an increase in intracellular calcium which rapidly reached a peak and returned to baseline within 60 s. The response was concentration dependent and unaffected by removal of extracellular calcium or addition of the inorganic channel blocker Ni2+. Similar transient responses were seen with histamine and angiotensin II and experiments monitoring manganese entry suggest that agonist responses in this cell line involve mainly release of calcium from intracellular stores. However, unlike bradykinin, the response to carbachol, at all concentrations, failed to return completely to baseline suggesting a small secondary influx component and highlighting possible differences between the mechanisms of calcium elevation by these two agonists.
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PMID:Agonist-induced changes in [Ca2+]i in N1E-115 cells: differential effects of bradykinin and carbachol. 163 11

The potential Ca2(+)-releasing activity of the inositol tetrakisphosphates Ins(1,3,4,6)P4 and DL-Ins(1,4,5,6)P4 and the inositol pentakisphosphate Ins(1,3,4,5,6)P5 and their effect on Ins(1,4,5)P3- and DL-Ins (1,3,4,5)P4-mediated Ca2+ release were examined in permeabilized SH-SY5Y human neuroblastoma cells. Neither DL-Ins(1,4,5,6)P4 nor Ins(1,3,4,5,6)P5 exhibit Ca2(+)-releasing activity at concentrations up to 10 microM, but Ins(1,3,4,6)P4 releases Ca2+ dose-dependently, with an EC50 value (conen, giving half-maximal effect) of 5.92 +/- 0.47 microM. Maximal response by this tetrakisphosphate (49 +/- 2.5%) is significantly less than that seen with Ins(1,4,5)P3 (60 +/- 3%) and is achieved at a concentration of 30 microM. In the presence of this concentration of Ins(1,3,4,6)P4 the EC50 value for Ins(1,4,5)P3-mediated Ca2+ release increases from 0.12 +/- 0.02 microM to 2.11 +/- 0.51 microM, providing evidence that this naturally occurring inositol tetrakisphosphate may recognize and exhibit its Ca2(+)-releasing activity via the Ins(1,4,5)P3 receptor. DL-Ins(1,3,4,5)P4, however, at its maximally effective concentration (10 microM) does not significantly affect Ins(1,4,5)P3-mediated Ca2+ release, and therefore appears to mediate its Ca2(+)-mobilizing action through a receptor distinct from that for Ins(1,4,5)P3.
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PMID:Interactions between inositol tris- and tetrakis-phosphates. Effects on intracellular Ca2+ mobilization in SH-SY5Y cells. 164 28

We have tested 36 patients with the Lambert-Eaton myasthenic syndrome for serum antibodies to voltage-gated calcium channels by using an immunoprecipitation assay with [125I] omega-conotoxin-labeled voltage-gated calcium channels extracted from a human neuroblastoma cell line, SKN-SH. Forty-four percent of these patients had significant levels of antibody (30-1,466 pM) compared with healthy control individuals (less than 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage-gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti-voltage-gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30-82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert-Eaton myasthenic syndrome.
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PMID:Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. 164 44

Intracellular Ca2+ stores in permeabilized SH-SY5Y neuroblastoma cells were mobilized by D-myo-inositol 1,4,5-trisphosphate [D-Ins(1,4,5)P3] and two of its synthetic analogues, DL-myo-inositol 1,4-bisphosphate 5-phosphorothioate (DL-InsP3-5S) and DL-myo-inositol 1,4,5-trisphosphorothioate (DL-InsP3S3). The concentrations of D-Ins(1,4,5)P3, DL-InsP3-5S, and DL-InsP3S3 required for half-maximal release were 0.11, 0.8, and 2.5 microM, respectively. All agents were full agonists, releasing 55-60% of sequestered 45Ca2+. D-Ins(1,4,5)P3-induced mobilization of Ca2+ was transient, and Ca2+ reuptake followed D-Ins(1,4,5)P3 metabolism closely. DL-InsP3S3-induced mobilization was persistent, consistent with the resistance of this analogue to metabolic enzymes. In contrast, DL-InsP3-5S-induced Ca2+ mobilization was followed by reuptake of Ca2+, albeit at a slower rate than that seen with D-Ins(1,4,5)P3. DL-InsP3-5S and DL-InsP3S3 were resistant to D-Ins(1,4,5)P3 5-phosphatase and potently inhibited the enzyme, with Ki values of 6.8 and 1.7 microM, respectively. DL-InsP3S3 was resistant to D-Ins(1,4,5)P3 3-kinase and was a very weak inhibitor of the enzyme (Ki = 230 microM). The ability of DL-InsP3-5S to inhibit D-Ins(1,4,5)P3 phosphorylation (apparent Ki = 5 microM) and its loss of Ca(2+)-releasing ability on incubation with D-Ins(1,4,5)P3 3-kinase suggest that this analogue may undergo phosphorylation to inositol 1,3,4-trisphosphate 5-phosphorothioate. These differential and complementary properties of DL-InsP3-5S and DL-InsP3S3 may be useful in dissecting the roles of D-Ins(1,4,5)P3 and D-myo-inositol 1,3,4,5-tetrakisphosphate in Ca2+ homeostasis.
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PMID:Synthetic phosphorothioate-containing analogues of inositol 1,4,5-trisphosphate mobilize intracellular Ca2+ stores and interact differentially with inositol 1,4,5-trisphosphate 5-phosphatase and 3-kinase. 164 49

Human neuroblastoma cells (SH-SY5Y) have two types of voltage-activated calcium channels, which are equivalent to the N and L types. Both types of calcium channels were equally blocked by lead in a concentration-dependent and reversible manner, with Ki congruent to 1 microM. This lead concentration is in the same order of magnitude as that found in the blood of children exhibiting neuropsychological disorders. Sodium and potassium channel currents were not significantly affected by lead at a concentration of 10 microM.
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PMID:Potent blocking action of lead on voltage-activated calcium channels in human neuroblastoma cells SH-SY5Y. 165 Feb 79

Application of bradykinin (Bk) to neuroblastoma x dorsal root ganglion (DRG) neurone hybrid cells (ND7/23) evoked an inward (depolarizing) current associated with an increase in membrane conductance. This response was antagonized by D-Arg0,Hyp3,Thi5,8,D-Phe7-Bk, but was not mimicked by des-Arg9-Bk, indicating the involvement of B2-receptors. The response was unaltered by replacement of extracellular Na+ by N-methylglucamine. Replacement of extracellular Cl by gluconate shifted the estimate reversal potential to a more positive value, while the use of potassium acetate filled recording electrodes shifted the reversal potential to a more negative value, and reduced the response amplitude, indicating the importance of Cl- in the response. This response to Bk was mimicked by the calcium ionophore ionomycin. Bk stimulated the formation of inositol 1,4,5-trisphosphate (IP3), and increased the release of arachidonic acid. In addition, Bk produced an increase in [Ca2+]i, as determined by microspectrofluorimetry. This was due to the release of Ca2+ from intracellular stores, since the response was unaltered when the cells were bathed in Ca(2+)-free solution. In summary, Bk depolarizes ND7/23 cells, probably through the activation of a chloride conductance. It seems likely that this is secondary to the rise in cytosolic Ca2+ concentration, due to the release of Ca2+ from internal stores by IP3. This Ca(2+)-activated chloride response is present in some sensory neurones, although its role in the activation of sensory neurones by Bk is at present unclear.
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PMID:Bradykinin evoked depolarization of a novel neuroblastoma x DRG neurone hybrid cell line (ND7/23). 165 Feb 81

Ras (p21) proteins are involved in the control of cell growth and differentiation, but the mechanism by which they exert these effects is not yet known. Here we present evidence that c-Ha-ras (p21(Gly-12)) and its oncogenic mutant T24-ras (p21(Val-12)) selectively induce omega-conotoxin and dihydropyridine-sensitive Ca2+ currents within a few hours after introduction into the cytoplasm of neuroblastoma x glioma hybrid cells. Whereas control cells exhibited a mean Ca2+ current of 250 pA, it amounted to 730 pA in cells pretreated with ras protein. In cells loaded with p21(Gly-12), the effect occurred after 2 hours and was terminated after 8 hours. In contrast, introduction of p21(Val-12) resulted in a prolonged delay (6 hours) of the effect which lasted for more than 24 hours. When ras proteins were preactivated with the non-hydrolysable GTP analog GppNHp, the time courses of both p21(Gly-12) and p21(Val-12) effects were fast and sustained, suggesting that in intact cells (i) the GDP/GTP exchange is faster for p21(Gly-12) compared to p21(Val-12) and (ii) inactivation of p21(Gly-12) is mediated by GAP-induced GTPase activity. T-type Ca2+ currents and K+ currents were unaffected by ras proteins.
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PMID:Ras proteins activate calcium channels in neuronal cells. 165 68

We have previously reported that endothelin (RT) receptor activation increases intracellular calcium concentrations ([Ca2+]i) in NG108-15 cells, a hybrid of rat glioma C6-BU-1 and mouse neuroblastoma N18TG2 cells. This study was designed to further explore the origin of the ET receptor and [Ca2+]i mobilization in the parent cell lines hybridized to form the NG108-15 cells. [125I]ET-1 bound to a single class of high affinity sites in C6-BU-1 cells with a KD value of 108pM and Bmax of 12,400 sites/cell. ET-1, ET-2, ET-3 and big ET inhibited [125I]ET-1 binding to C6-BU-1 cells with KD values of 0.074, 0.167, 261 and 187 nM, respectively. All ETs produced a rapid increase in [Ca2+]i in C6-Bu-1 cells. EC50 values for ET-1, ET-2, ET-3 and big ET were 0.71, 1.14, 120 and 243 nM respectively. There was a significant correlation between the KD values obtained from competition binding experiments and the EC50 values from [Ca2+]i response curves in C6-BU-1 cells (r = 0.996, p less than 0.004). Ten nM ET-1 produced about 85% of the maximal [Ca2+]i increase in C6-BU-1 cells which was reduced by 96% in the absence of extracellular calcium. Furthermore, diltiazem (10 microM) and nifedipine (1 microM) failed to block ET-induced [Ca2+]i mobilization. None of the ETs elevated [Ca2+]i or displayed any specific [125I]ET-1 binding in N18TG2 cells. These data suggest that ET binds to a specific ET receptor in C6-BU-1 cells, and elevates [Ca2+]i through dihydropyridine-insensitive, receptor-mediated calcium influx. Further, the ability of ETs to elevate [Ca2+]i in NG108-15 hybrid cells is due to the ET receptor inherent to the C6-BU-1 glioma parent line.
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PMID:Comparison of endothelin binding and calcium mobilization in C6-BU-1 rat glioma and N18TG2 mouse neuroblastoma cells. 165 31


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