Linked Life Data

1533269

Source:http://linkedlifedata.com/resource/pubmed/id/1533269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1992-5-26
pubmed:abstractText
Several competitive antagonists of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors are phosphonate analogs of L-glutamic acid. The position of the phosphonate has been shown to be important in the structure-activity relationships of these analogs. To investigate whether other phosphorous-containing compounds had activity at the NMDA receptor, several organophosphates were tested for the ability to inhibit the specific binding to brain synaptic membranes of 3-((+-)-2-carboxypiperazin-4-yl)-[1,2-3H]propyl-1-phosphonic acid ([3H]CPP), a selective antagonist of NMDA receptors. Diisopropylfluorophosphate (DFP), dichlorvos, cyanophos, mipafox, and o-ethyl o-4-nitrophenyl phenylphosphonothioate are relatively potent inhibitors of [3H]CPP binding to synaptic membranes. The inhibition produced by DFP is selective for the NMDA subtype of excitatory amino acid receptors, is irreversible, and can be prevented by preincubation with excess CPP, 2-amino-7-phosphonoheptanoic acid, or L-glutamate. Rat brain synaptic membranes have a population of phosphonate-sensitive [3H]DFP binding sites that are covalently labeled by [3H]DFP. Two protein bands of synaptic membrane proteins subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis are labeled by [3H]DFP in a 2-amino-5-phosphonopentanoic acid-sensitive manner. These proteins have an average molecular size of 47-50 and 32 kDa. Proteins of nearly identical molecular sizes have been shown in other studies to be components of an NMDA receptor complex. These observations are indicative of an interaction between the organophosphates and the NMDA receptor protein complex and suggest that DFP may be another important pharmacological tool that can be used in the elucidation of the molecular structure of the NMDA receptor complex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
750-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Characterization of organophosphate interactions at N-methyl-D-aspartate receptors in brain synaptic membranes.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.