Linked Life Data

10860922

Source:http://linkedlifedata.com/resource/pubmed/id/10860922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-8-10
pubmed:abstractText
The anticonvulsant alpha-ethyl, alpha-methyl-gamma-thiobutyrolactone (alphaEMTBL) potentiates the response to a submaximal concentration of glycine produced by receptors composed of human glycine alpha1-subunits but reduces the response of receptors composed of rat glycine alpha3-subunits. Both the potentiating and blocking actions of alphaEMTBL are reduced by higher concentrations of glycine. The subunit specificity of alphaEMTBL block is conferred by a residue in the second membrane-spanning region (M2), which is alanine in the alpha3-subunit (A254) and glycine in the alpha1-subunit. The mutation A254G in the alpha3-subunit removes blocking by alphaEMTBL and reveals potentiation. Picrotin, a picrotoxinin analog, blocks responses of receptors composed of either alpha1 or alpha3-subunits. Blocking of alpha3 receptors by picrotin is reduced in the presence of alphaEMTBL, indicating that the mechanisms interact at some point, but the mutation alpha3 A254G does not remove block by picrotin. However, mutation of a nearby residue alpha3 T258F does remove block by picrotin, picrotoxinin and alphaEMTBL. These observations suggest that alphaEMTBL and picrotin act on glycine alpha3 receptors to produce block by an allosteric mechanism that involves overlapping sets of residues in the M2 region. Coexpression of the alpha3-subunit with the beta-subunit of the glycine receptor also removes block by alphaEMTBL and reveals potentiation, suggesting that receptors containing either alpha3 or alpha1 glycine receptor subunits are potentiated in the adult brain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Subunit-specific action of an anticonvulsant thiobutyrolactone on recombinant glycine receptors involves a residue in the M2 membrane-spanning region.
pubmed:affiliation
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA. jhs@morpheus.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.