Sevoflurane inhibits the µ-opioid receptor function expressed in Xenopus oocytes

Pharmacology. 2011;88(3-4):127-32. doi: 10.1159/000330096. Epub 2011 Sep 6.

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.

MeSH terms

  • Aluminum Compounds / pharmacology
  • Analgesics, Opioid / pharmacology
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Female
  • Fluorides / pharmacology
  • GTP-Binding Protein alpha Subunits, Gq-G11 / physiology*
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Methyl Ethers / pharmacology*
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Protein Kinase Inhibitors / pharmacology
  • Receptors, Opioid, mu / antagonists & inhibitors*
  • Receptors, Opioid, mu / physiology
  • Recombinant Fusion Proteins / physiology*
  • Sevoflurane
  • Xenopus laevis

Substances

  • Aluminum Compounds
  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Indoles
  • Maleimides
  • Methyl Ethers
  • Protein Kinase Inhibitors
  • Receptors, Opioid, mu
  • Recombinant Fusion Proteins
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • tetrafluoroaluminate
  • Sevoflurane
  • Protein Kinase C
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • bisindolylmaleimide I
  • Fluorides