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