Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-9-18
pubmed:abstractText
The specific mechanisms underlying general anesthesia are primarily unknown. The intravenous general anesthetic etomidate acts by potentiating GABA(A) receptors, with selectivity for beta2 and beta3 subunit-containing receptors determined by a single asparagine residue. We generated a genetically modified mouse containing an etomidate-insensitive beta2 subunit (beta2 N265S) to determine the role of beta2 and beta3 subunits in etomidate-induced anesthesia. Loss of pedal withdrawal reflex and burst suppression in the electroencephalogram were still observed in the mutant mouse, indicating that loss of consciousness can be mediated purely through beta3-containing receptors. The sedation produced by subanesthetic doses of etomidate and during recovery from anesthesia was present only in wild-type mice, indicating that the beta2 subunit mediates the sedative properties of anesthetics. These findings show that anesthesia and sedation are mediated by distinct GABA(A) receptor subtypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8608-17
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:13679430-Anesthetics, pubmed-meshheading:13679430-Animals, pubmed-meshheading:13679430-Anticonvulsants, pubmed-meshheading:13679430-Behavior, Animal, pubmed-meshheading:13679430-Bicyclo Compounds, Heterocyclic, pubmed-meshheading:13679430-Binding, Competitive, pubmed-meshheading:13679430-Cell Separation, pubmed-meshheading:13679430-Consciousness, pubmed-meshheading:13679430-Dose-Response Relationship, Drug, pubmed-meshheading:13679430-Electroencephalography, pubmed-meshheading:13679430-Etomidate, pubmed-meshheading:13679430-Gene Targeting, pubmed-meshheading:13679430-Hypnotics and Sedatives, pubmed-meshheading:13679430-Male, pubmed-meshheading:13679430-Mice, pubmed-meshheading:13679430-Mice, Mutant Strains, pubmed-meshheading:13679430-Motor Activity, pubmed-meshheading:13679430-Patch-Clamp Techniques, pubmed-meshheading:13679430-Protein Isoforms, pubmed-meshheading:13679430-Purkinje Cells, pubmed-meshheading:13679430-Receptors, GABA-A, pubmed-meshheading:13679430-Recovery of Function, pubmed-meshheading:13679430-Triazoles
pubmed:year
2003
pubmed:articleTitle
Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms.
pubmed:affiliation
Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Harlow, Essex CM20 2QR, United Kingdom.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't