γ-aminobutyric acid type A receptor β2 subunit mediates the hypothermic effect of etomidate in mice

被引:26
作者
Cirone, J [1 ]
Rosahl, TW [1 ]
Reynolds, DS [1 ]
Newman, RJ [1 ]
O'Meara, GF [1 ]
Hutson, PH [1 ]
Wafford, KA [1 ]
机构
[1] Merck Sharp & Dohme Res Labs, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England
关键词
D O I
10.1097/00000542-200406000-00016
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background The authors have previously described that the gamma-aminobutyric acid type A (GABA(A)) receptor beta2N265S mutation results in a knock-in mouse with reduced sensitivity to etomidate. After recovery from etomidate anesthesia, these mice have improved motor performance and less slow wave sleep. Because most clinically used anesthetics produce hypothermia, the effect of this mutation on core body temperature was investigated. Methods: The effect of etomidate and propofol on core body temperature were measured using radiotelemetry in freely moving GABA(A) receptor beta2N265S mutant mice and wild-type controls. Results: beta2N265S mutant mice have a reduced hypothermic response to anesthetic doses of etomidate compared with wildtype controls and after a transient loss of righting reflex regain normothermia more rapidly compared with wild-type controls. Subanesthetic doses of etomidate produce hypothermia, which was not observed in the mutant mice. Vehicle administration resulted in a stress-induced hyperthermic response in both genotypes. Propofol produced a hypothermic response that was similar in both genotypes. Conclusions: The GABA(A) receptor beta2 subunit mediates a significant proportion of the hypothermic effects of etomidate. As the beta2 subunit mediates postrecovery ataxia and sedation, anesthetic agents that do not have in vivo potency at beta2 subunit-containing receptors offer the potential for surgical anesthesia with improved recovery characteristics.
引用
收藏
页码:1438 / 1445
页数:8
相关论文
共 36 条
[1]  
Arndt K, 1999, AORN J, V70, P204
[2]   The in vitro and in vivo enantio selectivity of etomidate implicates the GABAA receptor in general anaesthesia [J].
Belelli, D ;
Muntoni, AL ;
Merrywest, SD ;
Gentet, LJ ;
Casula, A ;
Callachan, H ;
Madau, P ;
Gemmell, DK ;
Hamilton, NM ;
Lambert, JJ ;
Sillar, KT ;
Peters, JA .
NEUROPHARMACOLOGY, 2003, 45 (01) :57-71
[3]   The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid [J].
Belelli, D ;
Lambert, JJ ;
Peters, JA ;
Wafford, K ;
Whiting, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :11031-11036
[4]   Deletion of the α1 or β2 subunit of GABAA receptors reduces actions of alcohol and other drugs [J].
Blednov, YA ;
Jung, S ;
Alva, H ;
Wallace, D ;
Rosahl, T ;
Whiting, PJ ;
Harris, RA .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (01) :30-36
[5]  
BLIGH J, 1981, FED PROC, V40, P2746
[6]   Hypothalamic neurons - Mechanisms of sensitivity to temperature [J].
Boulant, JA .
MOLECULAR MECHANISMS OF FEVER, 1998, 856 :108-115
[7]   ENDOCRINOLOGIC CHANGES FOLLOWING ETOMIDATE, MIDAZOLAM, OR METHOHEXITAL FOR MINOR SURGERY [J].
CROZIER, TA ;
BECK, D ;
SCHLAEGER, M ;
WUTTKE, W ;
KETTLER, D .
ANESTHESIOLOGY, 1987, 66 (05) :628-635
[8]  
Desborough JP, 1997, BRIT J HOSP MED, V57, P440
[9]   ANTI-ADRENAL ACTION OF A SUBANAESTHETIC DOSE OF ETOMIDATE [J].
DIAGO, MC ;
AMADO, JA ;
OTERO, M ;
LOPEZCORDOVILLA, JJ .
ANAESTHESIA, 1988, 43 (08) :644-645
[10]   Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events - A randomized clinical trial [J].
Frank, SM ;
Fleisher, LA ;
Breslow, MJ ;
Higgins, MS ;
Olson, KF ;
Kelly, S ;
Beattie, C .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (14) :1127-1134