%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 }