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

Mouse neuroblastoma cells of the clone N1E-115 express a variety of ion channels and receptors, including a number that is also involved in neurotransmission. Effects of Pb2+ on several of these ion channels have been investigated under experimental conditions that allow electrophysiological recording of membrane current carried by distinct types of ion channels. In whole-cell voltage clamp experiments voltage-dependent calcium channels are blocked by Pb2+ at micromolar concentrations, while voltage-dependent sodium channels are not affected by Pb2+. The neuronal type nicotinic acetylcholine (ACh) receptor-ion channel complex is sensitive to low concentrations of Pb2+. At 1 nM-3 microM, Pb2+ reduces the peak amplitude of the ACh-induced inward current to 74%-10% of the control value in a concentration-dependent manner. However, at Pb2+ concentration between 10 and 100 microM this blocking effect is reduced and kinetics of decay of the ACh-induced inward current are slowed. The effects of Pb2+ on the nicotinic receptor-mediated inward current amplitude can be described by the sum of two sigmoidal concentration-effect curves with an IC50 value of 19 nM and an EC50 of 21 microM. The serotonin 5-HT3 receptor-ion channel complex is less sensitive to Pb2+. The serotonin-induced inward current is blocked by Pb2+ with an IC50 value of 49 microM. In single channel patch clamp experiments internal Pb2+ causes activation of calcium-activated potassium channels in N1E-115 cells. The two types of calcium-activated potassium channels show differential sensitivity: the low conductance (SK) channel is more sensitive to Pb2+ than the high conductance (BK) channel. At micromolar concentrations Pb2+ also induces an ion current mediated by metal ion-activated ion channels. Opening of these channels, which have a single channel conductance of 24 pS and a reversal potential of 0 mV, depends on Pb2+ concentration. These effects of Pb2+ support the hypothesis that Pb2+ affects synaptic transmission by blocking presynaptic voltage-dependent calcium channels. On the other hand, effects on other sensitive target sites, the neuronal nicotinic ACh receptor in particular, clearly indicate that other targets may be involved in the toxic effects of Pb2+ on the nervous system.
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PMID:Differential neurotoxicological effects of lead on voltage-dependent and receptor-operated ion channels. 750 28

1. Pb2+ affects neuronal nicotinic acetylcholine receptors (nAChR) in N1E-115 neuroblastoma cells in a dual manner. At nanomolar concentrations a blockade is observed, while at submillimolar concentrations this blocking effect is reversed. 2. The Xenopus oocyte expression system was used to examine whether the dual effect of Pb2+ is related to a differential action on nAChR subtypes. Effects of Pb2+ were investigated in oocytes expressing nAChR after co-injection of alpha 3 and beta 2 or alpha 3 and beta 4 cDNA. 3. At 1-250 mumol/L, Pb2+ causes a 10-1000% increase of the response mediated by the alpha 3 beta 2 nAChR. 4. Pb2+ blocks ACh-induced inward currents mediated by alpha 3 beta 4 nAChR. The inhibitory potency of Pb2+ greatly varies between cells. In 50% of the cells concentrations < or = 1 mumol/L Pb2+ blocked the nicotinic response by 31-93%. In the other cells even at higher concentrations Pb2+ caused only 0-65% inhibition. 5. These results show that Pb2+ may both potentiate and block nAChR, depending on the type of nAChR subunit expressed.
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PMID:Subunit-dependent action of lead on neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. 755 31

1. The ability of various divalent metal ions to substitute for Ca2+ in activating distinct types of Ca(2+)-dependent K+ [K+(Ca2+)] channels has been investigated in excised, inside-out membrane patches of human erthrocytes and of clonal N1E-115 mouse neuroblastoma cells using the patch clamp technique. The effects of the various metal ions have been compared and related to the effects of Ca2+. 2. At concentrations between 1 and 100 microM Pb2+, Cd2+ and Co2+ activate intermediate conductance K+(Ca2+) channels in erythrocytes and large conductance K+(Ca2+) channels in neuroblastoma cells. Pb2+ and Co2+, but not Cd2+, activate small conductance K+(Ca2+) channels in neuroblastoma cells. Mg2+ and Fe2+ do not activate any of the K+(Ca2+) channels. 3. Rank orders of the potencies for K+(Ca2+) activation are Pb2+, Cd2+ > Ca2+, Co2+ >> Mg2+, Fe2+ for the intermediate erythrocyte K+(Ca2+) channel, and Pb2+, Cd2+ > Ca2+ > Co2+ >> Mg2+, Fe2+ for the small, and Pb2+ > Ca2+ > Co2+ >> Cd2+, Mg2+, Fe2+ for the large K+(Ca2+) channel in neuroblastoma cells. 4. At high concentrations Pb2+, Cd2+, and Co2+ block K+(Ca2+) channels in erythrocytes by reducing the opening frequency of the channels and by reducing the single channel amplitude. The potency orders of the two blocking effects are Pb2+ > Cd2+, Co2+ >> Ca2+, and Cd2+ > Pb2+, Co2+ >> Ca2+, respectively, and are distinct from the potency orders for activation. 5. It is concluded that the different subtypes of K+(Ca2+) channels contain distinct regulatory sites involved in metal ion binding and channel opening. The K+(Ca2+) channel in erythrocytes appears to contain additional metal ion interaction sites involved in channel block.
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PMID:Differential effects of heavy metal ions on Ca(2+)-dependent K+ channels. 764 Dec 41

The whole-cell version of patch clamping was used to compare the effects of acute in vitro exposure to inorganic lead (Pb2+) on voltage-sensitive calcium channels in cultured N1E-115 mouse neuroblastoma cells and E18 rat hippocampal neurons. Free Pb2+ concentrations in salines with a high lead-buffering capacity were measured with a calibrated Pb(2+)-selective electrode. Previously, we found that N1E-115 neurons contain low voltage activated, rapidly inactivating (T) channels and high voltage activated, slowly inactivating (L) channels. Pb2+ inhibits both channel subtypes in N1E-115 cells, with some selectivity against L-type channels (IC50 approximately 700 nM free Pb2+ for L-type channels, 1300 nM free Pb2+ for T-type channels; Audesirk and Audesirk, 1991). In addition to T-type and L-type channels, cultured E18 rat hippocampal neurons have been reported to contain high voltage-activated, rapidly inactivating (N) channels. In our experiments with 5 to 20 day old cultures, almost all neurons showed substantial L-type current, approximately half showed significant N-type current, and fewer than 5% showed significant T-type current. We found that Pb2+ is somewhat selective against L-type channels (IC50 approximately 30 nM free Pb2+ in 10 mM Ba2+ as the charge carrier, 55 nM in 50 mM Ba2+) compared to N-channels (IC50 approximately 80 nM free Pb2+ in 10 mM Ba2+, 200 nM in 50 mM Ba2+). These results suggest that the effects of Pb2+ on calcium channels of vertebrate neurons vary both among cell types and among channel subtypes.
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PMID:The effects of inorganic lead on voltage-sensitive calcium channels differ among cell types and among channel subtypes. 824 99

Lead exposure has devastating effects on the developing nervous system, producing morphological, cognitive, and behavioral deficits. To elucidate some of the mechanisms of lead neurotoxicity, we have examined its effects on the differentiation of several types of cultured neurons. Previously, we reported the effects of inorganic lead on several parameters of growth and differentiation of E18 rat hippocampal neurons and two types of neuroblastoma cells cultured in medium with 2% fetal calf serum (FCS) (Audesirk et al., 1991). In the present study, we report the effects of concentrations of lead ranging from 1nM to 1 mM on the differentiation of hippocampal neurons cultured in medium containing 10% FCS. In addition, we investigated lead effects on neurons isolated from the motor cortex region of the E18 rat embryo. Cortical neurons were exposed to lead in concentrations ranging from 0.1 nM to 1 mM in medium with either 10% FCS or 2% FCS for 48 hr. The effects of lead tended to be multimodal. Neurite initiation, which is highly sensitive to neurotoxic compounds, was inhibited by lead at both high and low concentrations, with no effects at intermediate levels. Medium with 10% FCS enhanced certain growth parameters and tended to reduce the effects of lead. There was an overall consistency in the effects of lead on motor cortex and hippocampal neurons.
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PMID:Effects of inorganic lead on the differentiation and growth of cortical neurons in culture. 824 6

Lead and cadmium contents were determined in representatively collected (commercial mills, wholesalers) samples of rye flour, breakfast cereals, porridge flakes, muesli cereals and pasta products. The samples were digested by heating them overnight in concentrated HNO3. Lead and cadmium concentrations were determined by GFAAS using a platform and (NH4)H2PO4 as a matrix modifier. ARC/CL coded wheat flour and other reference materials (NBS 1567a, BCR no. 189, BCR no. 191) were employed for the analytical quality control. Lead and cadmium contents found in the above samples were generally much lower than the present tolerance limits in Finland (300 micrograms/kg and 100 micrograms/kg respectively). The mean cadmium and lead contents of rye flours studied were very low, being 9 micrograms/kg and 16 micrograms/kg respectively. The mean contents of lead and cadmium in wheat-based breakfast cereals were 22 and 42, in rye products 19 and 26, in oats 17 and 2, in maize products 11 and 18 and in rice products 31 and 10 micrograms/kg, respectively. The mean contents of lead and cadmium in muesli cereals were 34 and 27 micrograms/kg. Remarkably high cadmium contents were found in some pastas made from imported durum wheat. The mean cadmium content of all past products was 79 micrograms/kg with a range of 26-182 micrograms/kg. Lead contents were low, with a mean of 18 micrograms/kg, and a range of 8 to 66 micrograms/kg. Cereals contribute about 59% of the average total dietary cadmium intake in Finland. Nearly 60% of the total cereal consumption is wheat and 27% rye. Since rye has a lower cadmium content than wheat, rye is preferable to wheat. About 15% of lead is derived from cereals. As the total intake of heavy metals is very low in Finland, there is no need to alter cereal consumption.
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PMID:Lead and cadmium in some cereal products on the Finnish market 1990-91. 831

Lead markedly amplified L-glutamate-induced oxidative stress, that is, increased L-glutamate-induced production of reactive oxygen species, decreased cellular glutathione, and induced cytotoxicity in human neuroblastoma cells. It was notable that oxidative burst induced by L-glutamate alone was observed only when neuronal glutathione was depleted. A role of protein kinase C (PKC) in glutamate-induced production of reactive oxygen species is likely because it was blocked by a PKC inhibitor. We suggest here that the mechanism whereby lead causes its neurotoxicity may be through the amplification of glutamate-induced oxidative stress, possibly through PKC activation.
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PMID:Lead amplifies glutamate-induced oxidative stress. 852 30

The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was used to record currents induced by serotonin at a concentration of 3 microM which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 microM and 2 microM, respectively. Lead and zinc suppressed the current with IC50S of 80 microM and 50 microM, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.
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PMID:Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells. 887 Sep 59

In cultured mouse neuroblastoma N1E-115 cells, inorganic lead (Pb2+) affects inward currents induced by activation of neuronal type nicotinic acetylcholine receptors (nAChR) in a biphasic manner. At nanomolar concentrations a blocking action is observed, while at submillimolar concentrations this blocking effect is reversed, resulting in a U-shaped concentration-effect curve. Maximal block by 90% is observed at 1-3 microM Pb2+. The interactions of Pb2+ with nAChR were examined at the blocking concentration of 10 nM Pb2+ and at 10 microM Pb2+, presenting the reversal of block. The fitted Emax for nAChR receptor activation by ACh was attenuated at both high and low Pb2+ concentrations by 24% and 54%, respectively. The EC50 values of the activation curves were not significantly altered; amounting to 53 microM, 64 microM and 86 microM ACh in the control situation and in the presence of 10 nM and 10 microM Pb2+, respectively. Further, receptor desensitization and ion channel block by ACh were also not affected by Pb2+. The results indicate that Pb2+ affects nAChR in a dual manner that involves inhibition and potentiation, both by non-competitive interactions. Neuronal nAChR expressed in N1E-115 cells resemble a combination of alpha 4 and beta 2 subunits, that constitute the predominant subunits in the central nervous system. The differential inhibition and potentiation of nAChR, together with the high sensitivity, are of interest with respect to Pb2+ neurotoxicity.
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PMID:Dual, non-competitive interaction of lead with neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells. 904 21

The aim of the study was to determine the major source and extent of metal pollution in a residential area of Greater Calcutta. In this area approximately 50,000 people reside in the vicinity of a lead factory that produces lead ingots and lead alloys. Many people, especially children, are affected by lead toxicity. Soils, waters, road dust, leaf dust, leaves and pond sediments were sampled in and around the factory area. Aliquots of the samples were mineralized with nitric acid and hydrogen peroxide in a microwave system. Lead and 19 other elements were quantified in the digests by inductively coupled plasma mass spectrometry. The performance of the procedure was confirmed by analyzing NBS-BCR standard reference soil, leaves, sediment samples. The soils are highly contaminated not only with lead (4.7%), but also with Cd (0.08%), Ag (0.001%), Cu (0.02%), Zn (1.0%), As (1.0%), Mo (0.003%), Sn (0.003%) and Hg (0.03%) (metal concentrations given in parentheses are maximum). Moving away from the smelter, most of metal concentrations, especially Pb, As, Mo, Cu, Hg, Zn, Cd, Sn and Ag, decreased exponentially over increasing distance. In the residential areas near the smelter, notably to the west side of the factory, metal concentrations significantly breached the threshold trigger values set in India by the Central Pollution Control Board (CPCB). Particulate materials from the smelter stack appear to contaminate soils up to at least 0.5 km. However, abnormally high metal levels in the immediate smelter area may be due to primarily fugitive emissions. The surface waters are only contaminated by arsenic ranges from 0.05 to 13.5 mg/l, but the ground water is currently not polluted by lead and arsenic. An appropriate treatment plant with some intervention measures should be taken to save the locality.
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PMID:Determination of lead and other metals in a residential area of greater Calcutta. 1023 82


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