Propofol Inhibits Muscarinic Acetylcholine Receptor-Mediated Signal Transduction in Xenopus Oocytes Expressing the Rat M1 Receptor

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Author(s)

Abstract

The effects of propofol, 2, 6-diisopropylphenol, an intravenous general anesthetic, on signal transduction mediated by the rat M1 muscarinic acetylcholine (ACh) receptor (M1 receptor) were examined in electrophysiological studies by analyzing receptor-stimulated, Ca<SUP>2+</SUP>-activated Cl<SUP>-</SUP>-current responses in the <I>Xenopus</I> oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca<SUP>2+</SUP>activated Cl<SUP>-</SUP> current, in a dose-dependent manner (EC<SUB>50</SUB>=114 nM). Propofol (5 - 50 μM) reversibly and dose-dependently inhibited induction of the Ca<SUP>2+</SUP>-activated Cl<SUP>-</SUP> current by ACh (100 nM) (IC<SUB>50</SUB>=5.6 μM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 μM) on the activation of current by injection of CaCl<SUB>2</SUB> and aluminum fluoride (AlF<SUB>4</SUB><SUP>-</SUP>). Propofol did not affect activation of the current by the intracellular injected Ca<SUP>2+</SUP>, or activation of the current by the intracellular injected AlF<SUB>4</SUB><SUP>-</SUP>. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca<SUP>2+</SUP> from Ca<SUP>2+</SUP> store or the Ca2<SUP>+</SUP>-activated Cl<SUP>-</SUP> channel. Propofol apparently inhibits the M1 receptor-mediated signal transduction at the receptor site and/or the site of interaction between the receptor and associated G protein.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 79(3), 319-325, 1999-03-01

    The Japanese Pharmacological Society

References:  25

Cited by:  3

Codes

  • NII Article ID (NAID)
    10008682806
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4699237
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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