Linked Life Data

1674587

Source:http://linkedlifedata.com/resource/pubmed/id/1674587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-6-21
pubmed:abstractText
It has been suggested that one of the effects of glycine at the N-methyl-D-aspartate (NMDA) receptor complex is to reduce the amount of apparent receptor desensitization. Thus, blockade with a glycine site antagonist results in NMDA responses that show an increased amount of fade. In agreement with this, we found that antagonism of NMDA-evoked whole-cell currents by 7-chlorokynurenic acid (7-Cl-KYNA) indeed resulted in NMDA responses that displayed an increased amount of fade. However, those responses that were antagonized by (+)-HA-966 showed the opposite, i.e., less tendency to fade. On examination of these responses, it appeared that those produced in the presence of (+)-HA-966 were slower in onset and faster in offset than control responses recorded in the presence of glycine alone. Kinetic analysis of the on- and off-rates of NMDA- and glutamate-evoked NMDA receptor-mediated responses revealed that these were markedly affected by (+)-HA-966 but only slightly by 7-Cl-KYNA. The decrease of the glutamate response decay time constant and the increase of the response rise time constant produced by (+)-HA-966 indicated that it reduced the affinity of glutamate for its recognition site on the NMDA receptor by 5-fold. These results suggest that binding of (+)-HA-966 to the glycine site on the NMDA receptor complex produces an allosteric reduction in the affinity of agonists for the glutamate recognition site, whereas 7-Cl-KYNA has relatively little effect and, thus, acts more as a pure antagonist at the glycine site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
666-70
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Effects of (+)-HA-966 and 7-chlorokynurenic acid on the kinetics of N-methyl-D-aspartate receptor agonist responses in rat cultured cortical neurons.
pubmed:affiliation
Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
pubmed:publicationType
Journal Article