Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1994-10-24
|
| pubmed:abstractText |
Neuronal injury induced by the excessive release of endogenous Zn2+ at central glutamatergic synapses may contribute to the pathogenesis of epileptic brain damage. We explored the possibility that N-methyl-D-aspartate receptors might be involved in Zn2+ neurotoxicity. Exposure of murine cortical cell cultures to 300-1000 microM concentrations of Zn2+ for 15 min resulted in widespread neuronal degeneration, accompanied by the release of lactate dehydrogenase to the bathing medium. Both non-competitive and competitive N-methyl-D-aspartate antagonists attenuated this degeneration. However, the participation of N-methyl-D-aspartate receptors in Zn2+ neurotoxicity was atypical. Removal of extracellular Ca2+ attenuated N-methyl-D-aspartate neurotoxicity but potentiated Zn2+ neurotoxicity, whereas increasing extracellular Ca2+ potentiated N-methyl-D-aspartate neurotoxicity but attenuated Zn2+ neurotoxicity. Furthermore, the nature of the antagonism of Zn2+ neurotoxicity induced by N-methyl-D-aspartate antagonists was qualitatively different from that seen with other N-methyl-D-aspartate receptor-mediated events. The block of Zn2+ neurotoxicity induced by the non-competitive N-methyl-D-aspartate antagonist MK-801 was better overcome by increasing Zn2+ concentration than the block induced by the competitive antagonists D-aminophosphonovalerate and CGS-19755. We hypothesize that N-methyl-D-aspartate receptor-gated channels contribute to Zn2+ toxicity by providing a route of Zn2+ influx into neurons. Consistent with this idea, intracellular Zn2+ visualized by the fluorescent Zn2+ chelator, N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide, rose during Zn2+ exposure; this rise was increased by N-methyl-D-aspartate and reduced by either N-methyl-D-aspartate antagonists or high Ca2+.2+ in neuronal cell homeostasis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0306-4522
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
60
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1049-57
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7936205-Animals,
pubmed-meshheading:7936205-Cell Death,
pubmed-meshheading:7936205-Cells, Cultured,
pubmed-meshheading:7936205-Cerebral Cortex,
pubmed-meshheading:7936205-Dose-Response Relationship, Drug,
pubmed-meshheading:7936205-Mice,
pubmed-meshheading:7936205-Mice, Inbred Strains,
pubmed-meshheading:7936205-N-Methylaspartate,
pubmed-meshheading:7936205-Nerve Degeneration,
pubmed-meshheading:7936205-Neurons,
pubmed-meshheading:7936205-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:7936205-Zinc
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
Zinc toxicity on cultured cortical neurons: involvement of N-methyl-D-aspartate receptors.
|
| pubmed:affiliation |
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110.
|
| pubmed:publicationType |
Journal Article
|