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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-5-14
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
747
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9042521-Acetylcholine,
pubmed-meshheading:9042521-Action Potentials,
pubmed-meshheading:9042521-Animals,
pubmed-meshheading:9042521-Brain Neoplasms,
pubmed-meshheading:9042521-Cell Line,
pubmed-meshheading:9042521-Electric Stimulation,
pubmed-meshheading:9042521-Electrophysiology,
pubmed-meshheading:9042521-Lead,
pubmed-meshheading:9042521-Membrane Potentials,
pubmed-meshheading:9042521-Mice,
pubmed-meshheading:9042521-Neuroblastoma,
pubmed-meshheading:9042521-Neurons,
pubmed-meshheading:9042521-Patch-Clamp Techniques,
pubmed-meshheading:9042521-Receptors, Nicotinic,
pubmed-meshheading:9042521-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Dual, non-competitive interaction of lead with neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells.
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pubmed:affiliation |
Research Institute of Toxicology, Utrecht University, Netherlands. m.oortgiesen@ritox.dgk.ruu.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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