title: Sevoflurane inhibits the µ-opioid receptor function expressed in Xenopus oocytes.
abstract: Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on μ-opioid receptor (μOR) functions is still unclear. In this study, the effects of sevoflurane on μOR functions were analyzed by using Xenopus oocytes expressing a μOR fused to chimeric Gα protein G(qi5) (μOR-G(qi5)). Sevoflurane by itself did not elicit any currents in oocytes expressing μOR-G(qi5), whereas sevoflurane inhibited the [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO)-induced Cl(-) currents at clinically used concentrations. Sevoflurane did not affect the Cl(-) currents induced by AlF(4)(-), which directly led to activation of G proteins. The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit μOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Jichi Medical University, Tochigi, Japan. kminami@med.uoeh-u.ac.jp
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Minami
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sudo
authors.forename: Toru
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Ogata
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D000077149:Sevoflurane; D014982:Xenopus laevis
chemical_list: D017607:Aluminum Compounds; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D007211:Indoles; D008301:Maleimides; D008738:Methyl Ethers; D047428:Protein Kinase Inhibitors; D017450:Receptors, Opioid, mu; D011993:Recombinant Fusion Proteins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C050992:tetrafluoroaluminate; D000077149:Sevoflurane; D011493:Protein Kinase C; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C070515:bisindolylmaleimide I; D005459:Fluorides