Linked Life Data

21498656

Source:http://linkedlifedata.com/resource/pubmed/id/21498656

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-6-20
pubmed:abstractText
Potentiating neuroactive steroids are potent and efficacious modulators of the GABA(A) receptor that act by allosterically enhancing channel activation elicited by GABA. Steroids interact with the membrane-spanning domains of the ? subunits of the receptor, whereas GABA binds to pockets in the interfaces between ? and ? subunits. Steroid interaction with a single site is known to be sufficient to produce potentiation, but it is not clear whether effects within the same ?-? pair mediate potentiation. Here, we have investigated whether the sites for GABA and steroids are functionally linked (i.e., whether the occupancy of a steroid site selectively affects activation elicited by GABA binding to the transmitter binding site within the same ?-? pair). For that, we used receptors formed of mutated concatenated subunits to selectively eliminate one of the two GABA sites and one of the two steroid sites. The data demonstrate that receptors containing a single functional GABA site are potentiated by the neurosteroid allopregnanolone regardless of whether the steroid interacts with the ? subunit from the same or the other ?-? pair. We conclude that steroids potentiate the opening of the GABA(A) receptor induced by either agonist binding site.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-86
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Occupation of either site for the neurosteroid allopregnanolone potentiates the opening of the GABAA receptor induced from either transmitter binding site.
pubmed:affiliation
Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural