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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1996-8-6
|
| pubmed:abstractText |
The pharmacologic specificity and anatomic distribution of [3H]dextrorphan recognition sites in the rat brain was characterized by quantitative autoradiography. Equilibrium saturation analysis indicated that [3H]dextrorphan labeled a single population of high affinity binding sites. These sites are heterogeneously distributed throughout rat forebrain with the following order of binding densities: hippocampal formation > cerebral cortex > thalamic nuclei > striatum. The association rate of [3H]dextrorphan with its binding site in area stratum radiatum of CA1 is accelerated by the addition of glycine and glutamate. [3H]Dextrorphan binding is, however, relatively insensitive to glycine and glutamate under equilibrium conditions, despite extensive prewashing procedures to deplete endogenous levels of these substances. The competitive N-methyl-D-aspartate (NMDA) antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and the glycine site antagonist 7-chlorokynurenic acid completely inhibit specific [3H]dextrorphan binding. D-AP5 suppresses [3H]dextrorphan binding in a regionally distinctive manner; a population of binding sites is weakly inhibited by D-AP5 in the lateral thalamic regions, whereas D-AP5 potently inhibits [3H]dextrorphan binding in the cerebral cortex. The rank order of potencies of an array of noncompetitive antagonists to inhibit [3H]dextrorphan binding unambiguously displays the pharmacologic profile of the noncompetitive antagonist domain of the NMDA receptor-channel complex. Furthermore, the distribution of [3H]dextrorphan binding sites in slide-mounted tissue appears qualitatively similar to the distribution of NMDA receptors previously reported using NMDA-displacement of [3H]glutamate, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) and [3H]1-[1-(2-thienyl)cyclohexyl]-piperidine (TCP) in most brain areas examined except the cerebellum. The molecular layer of the cerebellum displays a particularly high density of [3H]dextrorphan binding sites. The regional distribution of [3H]dextrorphan binding sites in rat brain does not correspond to the reported distributions of [3H]dextromethorphan or sigma binding sites.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
277
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1823-36
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8667254-Animals,
pubmed-meshheading:8667254-Autoradiography,
pubmed-meshheading:8667254-Binding Sites,
pubmed-meshheading:8667254-Brain,
pubmed-meshheading:8667254-Dextrorphan,
pubmed-meshheading:8667254-Dose-Response Relationship, Drug,
pubmed-meshheading:8667254-Glutamic Acid,
pubmed-meshheading:8667254-Male,
pubmed-meshheading:8667254-Rats,
pubmed-meshheading:8667254-Rats, Sprague-Dawley
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Regional distribution and characterization of [3H]dextrorphan binding sites in rat brain determined by quantitative autoradiography.
|
| pubmed:affiliation |
College of Pharmacy, Oregon State University, Corvallis, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|