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

Recent studies have shown that the calcium channel blockers, when combined with standard anticancer drugs, help overcome resistance that often develops to those drugs. Little is known about the effects of the calcium channel blockers themselves on tumor cells. We have studied the effects of one calcium channel blocker, verapamil, on human tumor cell lines in vitro. Our results show a reversible, antiproliferative action of verapamil on human medulloblastoma, pinealoblastoma, glioma, and neuroblastoma tumor lines established from pediatric patients. Growth rates are inhibited 10 to 100% by 10 to 100 microM verapamil with 50% inhibition occurring between 25 and 50 microM verapamil. No cell line proliferates in 100 microM verapamil, yet washing the cells after 72 h of incubation with 100 microM verapamil results in resumed cell growth. Growth inhibition is accompanied by dose-dependent decreases in DNA, RNA, and protein synthesis which occur within minutes after addition of verapamil. DNA flow cytometry on propidium iodide-stained nuclei shows that, after incubation for 48 h with 100 microM verapamil, the medulloblastoma and neuroblastoma tumor lines as well as normal, human foreskin and lung fibroblast cell lines are reversibly blocked throughout the cell cycle with slight increases in G1. Verapamil appears to have no effect on nucleic acid precursors or on calcium influx or efflux in human medulloblastoma cells.
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PMID:Antiproliferative effect of verapamil alone on brain tumor cells in vitro. 337 5

Effects of TI233, a calmodulin antagonist, on transmitter release were studied using a clonal pheochromocytoma cell line (PC12h). TI233, at a concentration of 30 microM, completely suppressed the release of preloaded [3H]NE and [3H]DA. The 50% suppression dose was around 3 microM. TI233 did not inhibit the [3H]NE release evoked by the calcium ionophore A23187. Electrophysiological examinations using a clonal neuroblastoma x glioma hybrid cell line (NG108-15) revealed that TI233 blocked the voltage-sensitive calcium channel of the membrane in the same concentration range. Thus it was suggested that TI233 inhibited transmitter release from neuronal cells by blocking the entry of calcium to the cytoplasm.
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PMID:Inhibition of transmitter release by TI233, a calmodulin antagonist, from clonal neural cells and a presumed site of action. 613 25

Voltage-sensitive calcium channels ( VSCCs ) have been identified in three clonal cells. These are the neuroblastoma X Chinese hamster brain hybrid ( NCB -20), the neuroblastoma X glioma hybrid (NG108-15), and the neuroblastoma ( N4TG1 ). Depolarization of NCB -20 cells with 50 mM KCl or 50 microM veratridine (VE) produced a 2- to 3-fold increase in net 45Ca2+ uptake. In NCB -20 cells, this voltage-sensitive 45Ca2+ uptake was inhibited selectively by organic calcium antagonists such as nitrendipine, cinnarizine, verapamil, and diltiazem (IC50 values = 6.4, 750, 1800, and 4500 nM, respectively). High K+-induced uptake was unaffected by 4-aminopyridine, tetraethylammonium, and tetrodotoxin (TTX), whereas VE-induced 45Ca2+ uptake was completely blocked by 3 microM TTX. In contrast to NCB -20 cells, NG108-15 cells showed a much smaller response to depolarizing stimuli. Following differentiation of NG108-15 cells by chronic treatment with 10 microM prostaglandin E1 and 50 microM 3-isobutyl-1-methylxanthine, depolarization induced a large increase in voltage-sensitive 45Ca2+ uptake. This induction was apparent after 24 hr and increased linearly for 96 hr. VSCC activity was also induced by 1.5% dimethyl sulfoxide and by other agents that increase intracellular cAMP, such as forskolin (1 microM) and cholera toxin (1 microgram/ml). Voltage-sensitive 45Ca2+ uptake in differentiated NG108-15 cells was inhibited by nitrendipine, D-600, and diltiazem (IC50 values = 7, 690, and 1600 nM). Our results suggest that VSCCs in neuronal clonal cell lines can be altered by cellular differentiation. In contrast to those VSCCs involved in neurotransmitter release, the VSCCs described here appear to be blocked by organic calcium channel antagonists at very low concentrations.
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PMID:Identification and characterization of voltage-sensitive calcium channels in neuronal clonal cell lines. 620 53

The dinoflagellate toxin maitotoxin (MTX) stimulated 45Ca2+ uptake in cultured NG108-15 neuroblastoma X glioma cells. Depolarizing stimuli (e.g., 50 mM K+) produced an immediate stimulation in Ca2+ uptake, whereas that produced by MTX occurred only after a lag period of about 2 min. MTX did not stimulate Ca2+ uptake into fibroblasts. Both 50 mM K+- and MTX-stimulated Ca2+ uptake was blocked by organic calcium channel antagonists (nitrendipine, D-600, diltiazem) at very low concentrations. Cd2+ was also a potent blocker. The novel dihydropyridine BAY K8644 enhanced Ca2+ uptake in the presence of 50 mM K+ but had no effect in 5 mM Ca2+. However, in the presence of MTX, BAY K8644 stimulated Ca2+ uptake in 5 mM K+. The effects of MTX were not blocked by tetrodotoxin but were decreased in Na+-free medium. MTX did not stimulate Na+ uptake into NG108-15 cells and did not alter [3H]nitrendipine binding to rat brain cortical synaptosomes. It is concluded that MTX may alter the voltage dependence of calcium-channel activation.
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PMID:Interactions of maitotoxin with voltage-sensitive calcium channels in cultured neuronal cells. 620 99

The effect of the nitric oxide donor SIN-1 on the membrane potential of cultured mouse neuroblastoma-rat glioma hybrid NG108-15 cells was investigated using the whole cell patch method. It has been reported that neurite formation can be induced in NG108-15 cells by adding of dibutyryl cyclic AMP to the culture medium. Using this system we found that SIN-1 has a selective inhibitory effect on the membrane potential of the calcium current which is concentration-dependent in the 1 mu M-100 microM range. This effect was transient and reversible, the same as seen with the calcium channel blocker nilvadipine at concentrations of 10 microM to 10 microM. At higher concentrations, ranging from 500 microM to 1 mM, however, SIN-1 also caused prolonged inhibition of the membrane potential of the sodium current. However, this effect was also reversible. These findings suggest that SIN-1 has a reversible inhibitory action on the membrane potentials of neurons.
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PMID:[Effects of the nitric oxide donor SIN-1 on the membrane potential of mouse neuroblastoma-rat glioma hybrid cells]. 757 41

The actions of two omega-conopeptides on high-voltage-activated calcium channel currents in differentiated human neuroblastoma IMR32 cells were investigated. Similar to the previously reported action of omega-conopeptide GVIA, omega-conopeptide MVIIA irreversibly blocks IMR32 HVA calcium channel currents at low concentrations. Unlike GVIA action, however, novel omega-conopeptide SNX-260 (iodinated MVIIC) reversibly blocks these currents, also at low concentrations, with an IC50 near 50 nM. Different omega-conopeptides may be potent blockers of HVA calcium channel currents yet act either reversibly or irreversibly in a single cell.
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PMID:Irreversible and reversible blockade of IMR32 calcium channel currents by synthetic MVIIA and iodinated MVIIC omega-conopeptides. 760 42

Voltage-activated calcium channel currents were recorded from differentiated human neuroblastoma cells. SK-N-SH-SY5Y (SH-SY5Y) line, using patch-clamp techniques. Experimental solutions were designed to suppress sodium and potassium channel currents, and barium ions were used as the charge carrier. Two distinct types of calcium channel currents (N- and L-like) were identified based on their time-dependent inactivation, pharmacology and single-channel conductances. N- and L-like calcium channel currents were evoked by step depolarizing pulses to potentials more positive than -40 mV from a holding potential of -100 mV. The N-like component showed time-dependent inactivation during maintained depolarization with a time constant of tau f approximately 100 ms, whereas the L-like currents showed very slow inactivation with a time constant of tau s approximately 1,000 ms. Steady-state inactivation of currents evoked from a holding potential of -100 mV had two distinct components. One component involved the reduction of the transient current and had a half-maximal current at approximately -66 mV, whereas the other component involved the reduction of the steady-state current in the range of -35 to 0 mV with a half-maximal current at approximately -17 mV. Bay K 8644 (5 microM), had two distinct actions, one was the increase (50%) of the current associated with a depolarizing pulse to +10 mV. The second action was the increase in the peak amplitude of the tail current and the slowing of the deactivation kinetics. Omega-conotoxin at 1 microM irreversibly reduced the N-like current, sparing a component that was still sensitive to 5 microM Bay K 8644. The single-channel currents recorded with the cell-attached configuration of the patch clamp revealed two distinct conductances: a large approximately 28 pS and a small approximately 16 pS, corresponding to the L- and N-like channels, respectively. Bay K 8644 at 5 microM increased the mean open time of L-like single channel currents without changing single-channel conductance.
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PMID:Two types of high voltage-activated calcium channels in SH-SY5Y human neuroblastoma cells. 768 Sep 40

The dorsal root ganglion-neuroblastoma cell line ND7-23 expresses low-voltage-activated calcium channel currents, and also expresses high-voltage-activated currents in about 50% of differentiated cells. Calcium channel currents were recorded with Ba2+ as the charge carrier. Low-voltage-activated currents were maximally activated at -30 mV and completely inactivated at holding potentials of -60 to -50 mV. omega-Conotoxin GVIA produced a reversible inhibition of low-voltage-activated currents, whereas the inhibition of high-voltage-activated current was largely irreversible. Dihydropyridine antagonists did not inhibit low-voltage-activated currents, whereas they inhibited a sustained, high-voltage-activated current. Low-voltage-activated currents were inhibited to a greater extent than high-voltage-activated currents by Ni2+ (100 microM) and by phenytoin (10 microM). Bradykinin (0.1 microM), baclofen (2 microM) and internal guanosine-5'-O-3-thiotriphosphate (100 microM) inhibited low-voltage-activated currents without affecting their kinetics of activation. Two classes of low-voltage-activated current were distinguished by their kinetics of inactivation. In the majority of cells, currents were slowly inactivating with a time-constant of inactivation of about 50 ms. They also exhibited a sustained component to the current, representing about 20% of the peak current. This component could be distinguished pharmacologically from high-voltage-activated current. The remainder of cells expressed a rapidly and completely inactivating current, with a time-constant of inactivation of about 20 ms. Two distinct single channel currents were observed in these cells, from cell-attached patch measurements, one had a single channel conductance of 7.9 pS, and the ensemble average current showed some inactivation. It is likely that this channel subtype underlies the low-voltage-activated current. The other showed long openings in the presence of a dihydropyridine agonist, had a conductance of 23.1 pS, and was non-inactivating.
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PMID:Low- and high-voltage-activated calcium channel currents and their modulation in the dorsal root ganglion cell line ND7-23. 790 87

Monoclonal antibodies that recognize skeletal muscle dihydropyridine-sensitive calcium channel subunits were used to identify similar proteins in neuronal and small cell carcinoma cell lines. alpha 1-related proteins were detected by FACS analysis on the surface of human neuroblastoma (IMR 32) and small cell carcinoma (DMS 273 and DMS 114) cell lines. alpha 1-like polypeptides from these cells were isolated and partially characterized. The polypeptides exhibit an M(r) similar to that of the L-type channel alpha 1 subunit and are recognized by two distinct anti-alpha 1 mAbs. The data provide biochemical evidence for structural similarities between the alpha 1 subunit of small cell carcinoma and neuronal cell lines. Similarly, an alpha 2-like protein was characterized from these cells. Because alpha 2 is a subunit shared by many subtypes of calcium channels, these data suggest that subunits other than the pore-forming alpha 1 subunit may play an important role in the etiology of Lambert-Eaton syndrome. We demonstrate directly that small cell carcinoma and a cell line derived from peripheral neurons share L-type calcium channel-related proteins and a protein common to many voltage-gated calcium channel subtypes. These data support a model that proposes that cross-reactivity of anti-tumor cell antibodies with presynaptic elements, possibly calcium channels, plays a role in the development of Lambert-Eaton syndrome.
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PMID:Alpha 1 and alpha 2 Ca2+ channel subunit expression in human neuronal and small cell carcinoma cells. 807 Jun 39

The voltage-dependent calcium channel current (ICa) in the neuroblastoma cell line of human origin (NB-I) was studied by the whole-cell clamp recording. Three types of ICa were identified in NB-I cells. Our electrophysiological and pharmacological findings have suggested that these three types of ICa are consistent with the T-, N- and L-type ICa, respectively. Phenytoin (PHT) inhibited T-type ICa by 13.0% at a concentration of 5 microM, and L-type ICa by 6.3% at a concentration of 100 microM. At a concentration of 100 microM, carbamazepine (CBZ) inhibited T- and L-type ICa by 6.0% and 5.9%, respectively. At a concentration of 50 microM, sodium valproate (VPA) blocked T- and L-type ICa by 6.1% and 47.5%, respectively. At a concentration of 50 microM, zomisamide (ZNS) inhibited T- and L-type ICa by 38.3% and 41.9%, respectively. Na+ channel blockade has been reported to be responsible for the clinical efficacy of PHT or CBZ. Inhibition of T-type ICa by PHT may enhance the efficacy of its anticonvulsant action. CBZ had little effect on ICa. The anticonvulsant activity may be related to the blockade of T-type ICa in the case of VPA and ZNS.
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PMID:Antiepileptic drugs--calcium current interaction in cultured human neuroblastoma cells. 808 41


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