Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1988-3-28
pubmed:abstractText
The central neurotoxicity of the endogenous tryptophan metabolite, quinolinate, has been postulated to participate in the pathogenesis of the neuronal cell loss associated with several neurological disease states. In the present study, quinolinate neurotoxicity was quantitatively studied in dissociated cell cultures prepared from the fetal mouse neocortex. Sufficient exposure of cortical cultures to quinolinate was associated with considerable neuronal cell loss, but no glial cell loss; this neurotoxicity could be blocked by 2-amino-5-phosphonovalerate and kynurenate, drugs known to block N-methyl-D-aspartate receptors. The quinolinate dose-toxicity relationship showed that the potency of quinolinate as a neurotoxin is relatively low, especially with brief (20 min) exposure times, where an ED50 of 2 mM was observed. However, with longer exposure times of 24 and 96 h, quinolinate is more potent: the latter exposure was characterized by an ED50 of 250-400 microM. Ion substitution experiments suggested that quinolinate neurotoxicity can be separated into two distinct components on the basis of differences in time course and ionic dependence: an acute, sodium-dependent "excitotoxic" component, marked by early cell swelling; and a late, calcium-dependent component, marked by delayed cell degeneration. Acute neuronal swelling was seen only with exposure to quinolinate concentrations in excess of 1 mM, so under actual pathophysiological conditions, quinolinate neurotoxicity might be nearly completely related to the calcium-dependent component, with little or no "excitotoxic" contribution.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Quinolinate neurotoxicity in cortical cell culture.
pubmed:affiliation
Department of Neurology, Stanford University Medical Center, CA 94305.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't