Linked Life Data

7509052

Source:http://linkedlifedata.com/resource/pubmed/id/7509052

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-3-21
pubmed:abstractText
There is widespread interest in the neurotoxicity of the endogenous excitatory amino acid neurotransmitter glutamate. Excessive glutamate release or accumulation leads to neuronal injury or death in a variety of experimental models of ischemia, anoxia and hypoglycemia. This injury appears to be caused by overactivation of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors since a variety of competitive and uncompetitive NMDA antagonists can attenuate this process, sometimes in a dramatic fashion. Given the clinical context in which this form of neuronal injury occurs, it would be desirable if we could identify agents that blocked NMDA toxicity, after initial receptor binding and ion channel fluxes had transpired. Because NMDA receptor activation initiates the arachidonic acid cascade, we have recently looked at whether the phospholipase A2 and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) can reduce NMDA neurotoxicity in vitro. In the concentration range 1-30 microM, NDGA diminished the death of cultured rodent hippocampal neurons produced by 100 microM NMDA. When 30 microM NDGA was present both before and after NMDA exposure, death declined by over 50%. NDGA did not block NMDA-induced inward currents in voltage-clamped neurons, so the drug is not a direct NMDA receptor antagonist. It also had no effect on the elevation in intracellular calcium produced by NMDA exposure. It is likely that NDGA acts at a site(s) distal to the NMDA receptor and the neuronal membrane to limit NMDA toxicity. We are hopeful that strategies for limiting excitotoxicity, which halt destructive intracellular events, can be developed for use in human neurological diseases linked to excessive stimulation of glutamate receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1279-88
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Nordihydroguaiaretic acid attenuates NMDA neurotoxicity--action beyond the receptor.
pubmed:affiliation
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.