Analysis of the Effects of Anesthetics and Ethanol on μ-Opioid Receptor

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Author(s)

Abstract

G protein–coupled receptors, in particular, Ca<SUP>2+</SUP>-mobilizing G<SUB>q</SUB>-coupled receptors have been reported to be targets for anesthetics. Opioids are commonly used analgesics in clinical practice, but the effects of anesthetics on the opioid <I>μ</I>-receptors (<I>μ</I>OR) have not been systematically examined. We report here an electrophysiological assay to analyze the effects of anesthetics and ethanol on the functions of <I>μ</I>OR in <I>Xenopus</I> oocytes expressing a <I>μ</I>OR fused to chimeric G<I>α</I> protein G<SUB>qi5</SUB> (<I>μ</I>OR-G<SUB>qi5</SUB>). Using this system, the effects of halothane, ketamine, propofol, and ethanol on the <I>μ</I>OR functions were analyzed. In oocytes expressing <I>μ</I>OR-G<SUB>qi5</SUB>, the<SUB> </SUB><I>μ</I>OR agonist DAMGO ([D-Ala<SUP>2</SUP>,<I>N</I>-MePhe<SUP>4</SUP>,Gly-ol]-enkephalin) elicited Ca<SUP>2+</SUP>-activated Cl<SUP>−</SUP> currents in a concentration-dependent manner (EC<SUB>50</SUB> = 0.24 <I>μ</I>M). Ketamine, propofol, halothane, and ethanol themselves did not elicit any currents in oocytes expressing <I>μ</I>OR-G<SUB>qi5</SUB>, whereas ketamine and ethanol inhibited the DAMGO-induced Cl<SUP>−</SUP> currents at clinically equivalent concentrations. Propofol and halothane inhibited the DAMGO-induced currents only at higher concentrations. These findings suggest that ketamine and ethanol may inhibit <I>μ</I>OR functions in clinical practice. We propose that the electrophysiological assay in <I>Xenopus</I> oocytes expressing <I>μ</I>OR-G<SUB>qi5</SUB> would be useful for analyzing the effects of anesthetics and analgesics on opioid receptor function.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 112(4), 424-431, 2010-04-20

    The Japanese Pharmacological Society

References:  39

Codes

  • NII Article ID (NAID)
    10027909045
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    13478613
  • NDL Article ID
    10651049
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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