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)

The increase in intracellular cyclic GMP concentrations in response to muscarinic-receptor activation in N1E-115 neuroblastoma cells is dependent on extracellular Ca2+ ion. The calcium ionophore A23187 can also evoke an increase in cyclic GMP in the presence of Ca2+ ion. Most (about 85%) of the guanylate cyclase activity of broken-cell preparations is found in the soluble fraction. The soluble enzyme can utilize MnGTP (Km = 55 micrometer), MgGTP (Km = 310 micrometer) and CaGTP (Km greater than 500 micrometer) as substrates. Free GTP is a strong competitive inhibitor (Ki approximately 20 micrometer). The enzyme possesses an allosteric binding site for free metal ions (Ca2+, Mg2+ and Mn2+). The membrane-bound guanylate cyclase is qualitatively similar to the soluble form, but has lower affinity for the metal-GTP substrates. Entry of Ca2+ into cells may increase cyclic GMP concentration by activating guanylate cyclase through an indirect mechanism.
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PMID:Regulation of synthesis of guanosine 3':5'-cyclic monophosphate in neuroblastoma cells. 3 71

The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of ""differentiated" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE1 and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3:5-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP protentiated the PGE1 effect in differentiated concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of Km and Vmax of neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE1 stimulated enzyme activity to GTP increase in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells.
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PMID:Effect of neurotransmitters, Guanosine triphosphate, and divalent ions on the regulation of adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate-induced "differentiated" neuroblastoma cells. 16 67

The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced "differentiated" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.
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PMID:Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in malignant and cyclic adenosine 3':5'-monophosphate-induced "differentiated" neuroblastoma cells. 23 30

1. Action potentials elicited in solutions with elevated [Ca2+] (1.8-40 mM) have been studied in differentiated cells of mouse neuroblastoma clone N1E-115 in tissue culture. 2. The action potential in high [Ca2+] solutions containing eithr Na+ or Tris is followed by a prolonged after-hyperpolarization (a.h.p.) lasting 0.5-4 sec. The a.h.p. reverses sign between -75 and -85 mV. 3. Externally applied tetraethylammonium (TEA, 15 mM) increases the Ca2+ spike overshoot, prolongs the falling phase and enhances the a.h.p. duration. The a.h.p. is inhibited by Ca2+ antagonists such as La3+, Co2+ and Mn2+. 4. After replacement of Ca2+ by Ba+ or Sr2+ (20mM) action potentials can still be elicited in Na+-free solution, but no a.h.p. is observed. 5. Increasing [Ca2+] from 1.8 up to 20 mM results in an increased capability of neuroblastoma cells to fire repetitively and in a consistent reduction of the firing rate from about 4-10 sec-1 to 0.5-1.8 sec-1. 6. It is concluded that Ca2+ entry during the action potential activates a TEA-resistant K+ conductance which gives rise to the prolonged a.h.p. Data from repetitively firing cells are consistent with the view that the a.h.p. plays a role in the regulation of low-frequency firing.
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PMID:The calcium action potential and a prolonged calcium dependent after-hyperpolarization in mouse neuroblastoma cells. 49 Mar 57

Electrical excitability is one of the various neuronal properties of neuroblastoma X glioma hybrid cells. At a Ca2+ concentration of 1.8 mM the action potential is inhibited by tetrodotoxin, suggesting that the inward current is carried by Na+ ions. In contrast, at a Ca2+ concentration of 20-36 mM and even in the absence of Na+, spikes (sometimes repetitive) with strong hyperpolarizing afterpotential occur, which are no longer affected by tetrodotoxin. They are, however, blocked by antagonists of Ca2+ like La3+, Co2+, Mn2+, and the synthetic compounds D-600 and BAY a-1040. This seems to indicate that at high concentrations of Ca2+, the inward current of the action potential is essentially carried by Ca2+. Sr2+, but not Mg2+ can effectively substitute for Ca2+. It slows down the time course of the action potential. Ba2+ depolarizes the membrane gradually. If Ca2+ is also present, Ba2+ causes a reduced depolarization and spontaneous action potentials with no hyperpolarizing after-potential are observed.
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PMID:Influence of cations on the electrical activity of neuroblastoma X glioma hybrid cells. 89 Apr 47

1. Pharmacological and kinetic properties of high-voltage-activated (HVA) Ca2+ channel currents were studied using the whole-cell and perforated patch-clamp methods in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, differentiated by dibutyryl cyclic AMP or by prostaglandin E1 and theophylline. 2. The HVA currents were separated into two components by use of two organic Ca2+ channel antagonists, omega-conotoxin GVIA (omega CgTX) and a dihydropyridine (DHP) compound, nifedipine. One current component, IDHP, was blocked by nifedipine (Kd = 8.2 nM) and was resistant to omega CgTX. Conversely, the other component, I omega CgTX, was irreversibly blocked by omega CgTX and was resistant to DHPs. Thus, IDHP could be studied in isolation by a short application of omega CgTX, while I omega CgTX could be studied in the presence of nifedipine. 3. The voltage for half-activation of IDHP was smaller than that of I omega CgTX by 13 mV. IDHP was activated at potentials that were subthreshold for voltage-dependent K+ currents of the cell, whereas I omega CgTX was not. 4. Time courses of activation and deactivation of IDHP were faster than those of I omega CgTX. 5. Voltage-dependent inactivation was small for both IDHP and I omega CgTX at any potential. 6. Ca(2+)-dependent inactivation of IDHP was faster and more prominent than that of I omega CgTX. The time course of the Ca(2+)-dependent inactivation of IDHP, but not I omega CgTX, was slowed as the membrane potential was made more positive between -20 and 30 mV, although amplitude of the current was increased. 7. Alkaline earth metal ions carried the two components of IHVA in the same order: Ba2+ greater than Sr2+ greater than Ca2+. 8. Metal ions blocked the two components of IHVA in the same order of potency: Gd3+ greater than La3+ greater than Cd2+ greater than Cu2+ greater than Mn2+ greater than Ni2+. 9. An alkylating agent, N-ethylmaleimide (NEM, 0.1 mM), selectively augmented IDHP by 30%. 10. During the course of cellular differentiation induced by dibutyryl cyclic AMP, IDHP appeared earlier than I omega CgTX. 11. These results indicate that two classes of Ca2+ channels contribute to the HVA currents of this cell line. The DHP-sensitive channel is more apt to generate Ca2+ spikes and Ca2+ plateau potentials than the omega CgTX-sensitive channel.
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PMID:Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a mammalian neuroblastoma-glioma cell line. 137 34

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 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

We characterized in membranes from the human neuroblastoma cell line NB-OK-1, an ANP-R1 receptor (Mr 130 kDa) for the atrial natriuretic peptide (ANP). This receptor recognized biologically active forms of ANP with high affinity but showed no affinity for truncated ANP forms. It was functional in that binding correlated with guanylate cyclase activation (a 2-fold increase in Vmax) with the following rank order of potency: rat ANP-(99-126) greater than human ANP-(99-126) greater than human ANP-(102-126) greater than porcine BNP (brain natriuretic peptide). The enzyme required free Mn2+ in addition to the Mn-GTP substrate (Km of about 0.3 mM for both basal and ANP-stimulated activity). In the presence of dithiothreitol, the dose-response curve of guanylate cyclase activation was shifted rightward by a factor of 30. ANP-R1 receptors were upregulated through protein synthesis in cells exposed to 1 mM carbamylcholine or 1 mM dibutyryl cyclic AMP for 8-24 h (ANP was ineffective).
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PMID:Characterization and regulation of atrial natriuretic peptide (ANP)-R1 receptors in the human neuroblastoma cell line NB-OK-1. 168 Jul 22

1. The effect of micromolar concentrations of divalent metal cations on ion current activated by 5-hydroxytryptamine (5-HT) was investigated in NCB-20 neuroblastoma cells by the use of the whole-cell, patch-clamp technique. 2. Ion current activated by 5-HT in these cells was mimicked by 5-HT3 receptor agonists, blocked by nanomolar concentrations of selective 5-HT3 receptor antagonists and reversed polarity at approximately 0 mV. These properties indicate that this current is carried primarily if not exclusively by the nonspecific cation channel activated by the 5-HT3 receptor. 3. The Group IIb metal cations Cd2+ and Zn2+ and the Group Ib cation Cu2+ inhibited 5-HT-activated current with inhibition increasing in a concentration-dependent manner over micromolar concentrations of the ions. The order of potency of the ions for inhibiting 5-HT-activated current was Zn2+ (IC50 = 20 microM) greater than or equal to Cu2+ (IC50 = 25 microM) greater than Cd2+ (IC50 = 75 microM) at -50 mV. The other divalent metal cations tested (Ba2+, Co2+, Mg2+, Mn2+, and Ni2+) produced little or no inhibition of 5-HT-activated current at concentrations up to 200 microM. 4. Inhibition of 5-HT-activated current by Cd2+ and Zn2+ was dependent on membrane potential with the Kd increasing e-fold per 72 and 52 mV, respectively. Inhibition by Cu2+ was much less voltage dependent with the Kd increasing e-fold per 233 mV. 5. Inhibition by all three cations decreased with increasing concentration of agonist over a range of 5-HT concentrations from 1 to 10 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of 5-HT3 receptor-mediated ion current by divalent metal cations in NCB-20 neuroblastoma cells. 172 46

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