The GABA-A beta3 subunit mediates anaesthesia induced by etomidate.
The i.v. agent etomidate exerts its anaesthetic actions through potentiation of gamma-aminobutyric acid-A receptors containing beta2 and beta3 subunits. It was recently shown that the beta2 subunit contributes to the sedative properties of etomidate, whereas the beta3 subunit is responsible for its anaesthetic properties. However, these studies evaluated anaesthetic effects in point mutation mice in which the effect of etomidate was decreased, but not abolished, at the beta2 subunit. Here we have used beta2 knockout mice to completely remove any contribution of the beta2 subunit to the effects of etomidate. Etomidate was equally anaesthetic in wildtype and knockout mice, thus further confirming that efficacy at the beta3 subunit only is sufficient to induce general anaesthesia.
O'Meara
Gillian F
GF
Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK.
Newman
Richard J
RJ
Fradley
Rosa L
RL
Dawson
Gerard R
GR
Reynolds
David S
DS
D000758:Anesthesia; D018686:Anesthetics, Intravenous; D000818:Animals; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D005045:Etomidate; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology*; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018686:Anesthetics, Intravenous; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005045:Etomidate