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Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol


Zeller, A; Arras, M; Lazaris, A; Jurd, R; Rudolph, U (2005). Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol. FASEB Journal, 19(12):1677-1679.

Abstract

General anesthetics are among the most widely used and important therapeutic agents. The molecular targets mediating different endpoints of the anesthetic state in vivo are currently largely unknown. The analysis of mice carrying point mutations in neurotransmitter receptor subunits is a powerful tool to assess the contribution of the respective receptor subtype to the pharmacological actions of clinically used general anesthetics. We examined the involvement of beta3-containing GABA(A) receptors in the respiratory, cardiovascular, hypothermic, and sedative actions of etomidate and propofol using beta3(N265M) knock-in mice carrying etomidate- and propofol-insensitive beta3-containing GABA(A) receptors. Although the respiratory depressant action of etomidate and propofol, as determined by blood gas analysis, was almost absent in beta3(N265M) mice, the cardiac depressant and hypothermic effects, as determined by radiotelemetry, and the sedative effect, as determined by decrease of motor activity, were still present. Taken together with previous findings, our results show that both immobilization and respiratory depression are mediated by beta3-containing GABA(A) receptors, hypnosis by both beta3- and beta2-containing GABA(A) receptors, while the hypothermic, cardiac depressant, and sedative actions are largely independent of beta3-containing GABA(A) receptors.

General anesthetics are among the most widely used and important therapeutic agents. The molecular targets mediating different endpoints of the anesthetic state in vivo are currently largely unknown. The analysis of mice carrying point mutations in neurotransmitter receptor subunits is a powerful tool to assess the contribution of the respective receptor subtype to the pharmacological actions of clinically used general anesthetics. We examined the involvement of beta3-containing GABA(A) receptors in the respiratory, cardiovascular, hypothermic, and sedative actions of etomidate and propofol using beta3(N265M) knock-in mice carrying etomidate- and propofol-insensitive beta3-containing GABA(A) receptors. Although the respiratory depressant action of etomidate and propofol, as determined by blood gas analysis, was almost absent in beta3(N265M) mice, the cardiac depressant and hypothermic effects, as determined by radiotelemetry, and the sedative effect, as determined by decrease of motor activity, were still present. Taken together with previous findings, our results show that both immobilization and respiratory depression are mediated by beta3-containing GABA(A) receptors, hypnosis by both beta3- and beta2-containing GABA(A) receptors, while the hypothermic, cardiac depressant, and sedative actions are largely independent of beta3-containing GABA(A) receptors.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Laboratory Animal Science
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2005
Deposited On:23 Mar 2009 09:22
Last Modified:05 Apr 2016 12:51
Publisher:Federation of American Societies for Experimental Biology
ISSN:0892-6638
Publisher DOI:10.1096/fj.04-3443fje
PubMed ID:16046472
Permanent URL: http://doi.org/10.5167/uzh-10872

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