title: The effects of anesthetics and ethanol on alpha2 adrenoceptor subtypes expressed with G protein-coupled inwardly rectifying potassium channels in Xenopus oocytes.
abstract: A wide range of physiological effects are mediated by alpha2-adrenoceptors (ARs) through their association with G protein-coupled inwardly rectifying potassium (GIRK) channels. Although alpha2-ARs are divided into three subtypes (alpha2A-C), a pharmacological distinction among the subtypes is difficult to establish because of the lack of a selective agonist and antagonist; therefore, little is known about the effects of anesthetics on the alpha2-AR subtypes. We expressed each subtype together with GIRK1/GIRK2 subunits in Xenopus oocytes and observed alpha2-AR-mediated GIRK1/GIRK2 currents to test the effects of ethanol, halothane, and several IV anesthetics at clinical concentrations. UK 14,304, a selective alpha2-AR agonist, evoked GIRK1/GIRK2 currents in every subtype. None of the IV anesthetics, which included pentobarbital, propofol, ketamine, and alphaxalone, influenced UK 14,304-evoked potassium currents in any of the receptor subtypes. Ethanol enhanced the UK 14,304-evoked potassium currents, whereas halothane inhibited the currents. However, these effects were not significantly different from those on the baseline-GIRK1/GIRK2 current, suggesting that neither ethanol nor halothane acts directly on the alpha2-AR subtypes. Although none of the drugs examined had any effect on the alpha2-ARs, the physiological actions of the alpha2-ARs mediated by the GIRK1/GIRK2 channels may be affected by ethanol and halothane.
authors.affiliation: *Waggoner Center for Alcohol and Addiction Research and Institute for Cellular and Molecular Biology, University of Texas at Austin; †Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu; and ‡Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamakura
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Sata
authors.forename: R Adron
authors.initials: RA
authors.lastname: Harris
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000187:drug effects*; D014982:Xenopus laevis
chemical_list: D000777:Anesthetics; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000431:Ethanol; D000068438:Brimonidine Tartrate