Activation of alpha 2B-adrenoceptors mediates the cardiovascular
effects of etomidate
A. Paris, M. Philipp, P. Tonner, M. Steinfath, M. Lohse, J. Scholz, and L. Hein. Anesthesiology, 99 (4):
889-95(October 2003)Paris, Andrea Philipp, Melanie Tonner, Peter H Steinfath, Markus
Lohse, Martin Scholz, Jens Hein, Lutz Comparative Study Research
Support, Non-U.S. Gov't United States Anesthesiology Anesthesiology.
2003 Oct;99(4):889-95..
Abstract
BACKGROUND: The intravenous anesthetic etomidate exhibits structural
similarities to specific alpha2-adrenoceptor agonists of the type
such as dexmedetomidine. The current study was performed to elucidate
the possible interaction of etomidate with alpha2-adrenoceptors in
mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO).
METHODS: Sedative and cardiovascular responses to etomidate and the
alpha2-agonist, dexmedetomidine, were determined in mice deficient
in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor
antagonist 3HRX821002 to recombinant alpha2-receptors by etomidate
was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS:
In vivo, loss and recovery of the righting reflex required similar
times after intraperitoneal injection of etomidate in wild-type and
in alpha2A-receptor-deficient mice, indicating that the hypnotic
effect of etomidate in mice does not require the alpha2A-receptor
subtype. Intravenous injection of etomidate resulted in a transient
increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in
wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure
in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells
transfected with alpha2-receptors, etomidate inhibited binding of
the alpha2-antagonist, 3HRX821002, with higher potency from alpha2B-
and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208
microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing
HEK293 cells, etomidate rapidly increased phosphorylation of the
extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results
indicate that etomidate acts as an agonist at alpha2-adrenoceptors,
which appears in vivo primarily as an alpha2B-receptor-mediated increase
in blood pressure. This effect of etomidate may contribute to the
cardiovascular stability of patients after induction of anesthesia
with etomidate.
Paris, Andrea Philipp, Melanie Tonner, Peter H Steinfath, Markus
Lohse, Martin Scholz, Jens Hein, Lutz Comparative Study Research
Support, Non-U.S. Gov't United States Anesthesiology Anesthesiology.
2003 Oct;99(4):889-95.
%0 Journal Article
%1 Paris2003
%A Paris, A.
%A Philipp, M.
%A Tonner, P. H.
%A Steinfath, M.
%A Lohse, M.
%A Scholz, J.
%A Hein, L.
%D 2003
%J Anesthesiology
%K Animals Blood Cardiovascular Cell Dose-Response Drug Etomidate/*pharmacology Heart Humans Knockout Line Male Mice Pressure/drug Rate/drug Relationship, System/*drug alpha-2/deficiency/genetics/*metabolism effects/*metabolism effects/physiology Receptor Adrenergic
%N 4
%P 889-95
%T Activation of alpha 2B-adrenoceptors mediates the cardiovascular
effects of etomidate
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14508322
%V 99
%X BACKGROUND: The intravenous anesthetic etomidate exhibits structural
similarities to specific alpha2-adrenoceptor agonists of the type
such as dexmedetomidine. The current study was performed to elucidate
the possible interaction of etomidate with alpha2-adrenoceptors in
mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO).
METHODS: Sedative and cardiovascular responses to etomidate and the
alpha2-agonist, dexmedetomidine, were determined in mice deficient
in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor
antagonist 3HRX821002 to recombinant alpha2-receptors by etomidate
was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS:
In vivo, loss and recovery of the righting reflex required similar
times after intraperitoneal injection of etomidate in wild-type and
in alpha2A-receptor-deficient mice, indicating that the hypnotic
effect of etomidate in mice does not require the alpha2A-receptor
subtype. Intravenous injection of etomidate resulted in a transient
increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in
wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure
in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells
transfected with alpha2-receptors, etomidate inhibited binding of
the alpha2-antagonist, 3HRX821002, with higher potency from alpha2B-
and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208
microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing
HEK293 cells, etomidate rapidly increased phosphorylation of the
extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results
indicate that etomidate acts as an agonist at alpha2-adrenoceptors,
which appears in vivo primarily as an alpha2B-receptor-mediated increase
in blood pressure. This effect of etomidate may contribute to the
cardiovascular stability of patients after induction of anesthesia
with etomidate.
@article{Paris2003,
abstract = {BACKGROUND: The intravenous anesthetic etomidate exhibits structural
similarities to specific alpha2-adrenoceptor agonists of the type
such as dexmedetomidine. The current study was performed to elucidate
the possible interaction of etomidate with alpha2-adrenoceptors in
mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO).
METHODS: Sedative and cardiovascular responses to etomidate and the
alpha2-agonist, dexmedetomidine, were determined in mice deficient
in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor
antagonist [3H]RX821002 to recombinant alpha2-receptors by etomidate
was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS:
In vivo, loss and recovery of the righting reflex required similar
times after intraperitoneal injection of etomidate in wild-type and
in alpha2A-receptor-deficient mice, indicating that the hypnotic
effect of etomidate in mice does not require the alpha2A-receptor
subtype. Intravenous injection of etomidate resulted in a transient
increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in
wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure
in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells
transfected with alpha2-receptors, etomidate inhibited binding of
the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B-
and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208
microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing
HEK293 cells, etomidate rapidly increased phosphorylation of the
extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results
indicate that etomidate acts as an agonist at alpha2-adrenoceptors,
which appears in vivo primarily as an alpha2B-receptor-mediated increase
in blood pressure. This effect of etomidate may contribute to the
cardiovascular stability of patients after induction of anesthesia
with etomidate.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Paris, A. and Philipp, M. and Tonner, P. H. and Steinfath, M. and Lohse, M. and Scholz, J. and Hein, L.},
biburl = {https://www.bibsonomy.org/bibtex/2552ea1a89cb4d385d340bd8c93dfd209/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {5b9603797fd69a678c8f3da63329394a},
intrahash = {552ea1a89cb4d385d340bd8c93dfd209},
issn = {0003-3022 (Print) 0003-3022 (Linking)},
journal = {Anesthesiology},
keywords = {Animals Blood Cardiovascular Cell Dose-Response Drug Etomidate/*pharmacology Heart Humans Knockout Line Male Mice Pressure/drug Rate/drug Relationship, System/*drug alpha-2/deficiency/genetics/*metabolism effects/*metabolism effects/physiology Receptor Adrenergic},
month = Oct,
note = {Paris, Andrea Philipp, Melanie Tonner, Peter H Steinfath, Markus
Lohse, Martin Scholz, Jens Hein, Lutz Comparative Study Research
Support, Non-U.S. Gov't United States Anesthesiology Anesthesiology.
2003 Oct;99(4):889-95.},
number = 4,
pages = {889-95},
shorttitle = {Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects
of etomidate},
timestamp = {2010-12-14T18:22:41.000+0100},
title = {Activation of alpha 2B-adrenoceptors mediates the cardiovascular
effects of etomidate},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14508322},
volume = 99,
year = 2003
}