Linked Life Data

20638393

Source:http://linkedlifedata.com/resource/pubmed/id/20638393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-9-27
pubmed:abstractText
The effects of benzodiazepines on GABA(A) receptors are dependent largely on the particular ? subunit isoform that is present in the receptor pentamer. The inclusion of either the ?4 or ?6 subunit is generally thought to render the receptor insensitive to classical benzodiazepines. We expressed the rat ?4?3?2L subtype in Xenopus oocytes and observed that both diazepam and flunitrazepam significantly potentiated GABA-gated currents. This potentiation occurred at nanomolar concentrations similar to those seen at the most abundant "diazepam-sensitive" receptor i.e., the ?1?2?2 subtype. In the ?4?3?2L receptor, the effects of diazepam and flunitrazepam were inhibited by nanomolar concentrations of the benzodiazepine site antagonists, Ro15-1788 and ZK93426. The presence of the ?3 subunit appears to be important for this modulation since diazepam did not affect GABA responses mediated by recombinant ?4?1?2L or ?4?2?2L receptors. Interestingly, when the ?4?3?2L receptor was expressed in HEK293 cells, diazepam and flunitrazepam displaced the relatively non-selective benzodiazepine site ligand, [(3)H]Ro15-4513, only at high concentrations (>10 ?M) demonstrating a lack of high affinity binding for these classical benzodiazepines. Functional studies of the cell-expressed receptors using whole cell recording techniques showed that neither diazepam nor flunitrazepam potentiated GABA-evoked currents although currents were enhanced by nanomolar concentrations of Ro15-4513. These results suggest that the observed benzodiazepine modulation of the ?4?3?2L subtype depends on the expression system used and may be specific for expression in Xenopus oocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-7064
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
527-33
pubmed:dateRevised
2011-2-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Benzodiazepine modulation of the rat GABAA receptor ?4?3?2L subtype expressed in Xenopus oocytes.
pubmed:affiliation
Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't