Jpn. J. Pharmacol. 79 (3), 319-325 (1999)


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

Yoshihisa Nagase (1,2), Muneshige Kaibara (1,*), Yasuhito Uezono (3), Futoshi Izumi (3), Koji Sumikawa (2) and Kohtaro Taniyama (1)


Department of (1) Pharmacology and (2) Anesthesiology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
(3) Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan
(*) To whom correspondence should be addressed.

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, Ca2+-activated Cl--current responses in the Xenopus oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca2+activated Cl- current, in a dose-dependent manner (EC50=114 nM). Propofol (5 - 50 microM) reversibly and dose-dependently inhibited induction of the Ca2+-activated Cl- current by ACh (100 nM) (IC50=5.6 microM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 microM) on the activation of current by injection of CaCl2 and aluminum fluoride (AIF4-). Propofol did not affect activation of the current by the intracellular injected Ca2+, or activation of the current by the intracellular injected AIF4-. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca2+ from Ca2+ store or the Ca2+-activated Cl- 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.


Keywords: Propofol, Muscarinic receptor, m1 Receptor, Xenopus oocyte, G protein


Copyrightę The Japanese Pharmacological Society 1999

[Back to TOC]