Pertussis toxin-sensitive g proteins mediate carbachol induced rem
sleep and respiratory depression.
Shuman, S. L., M. L. Capece, H. A. Baghdoyan, and R. Lydic.
Department of Anesthesia, The Pennsylvania State University,
College of Medicine, Hershey, Pennsylvania 17033
APStracts 2:0073R, 1995.
Microinjecting cholinomimetics into the medial pontine reticular
formation (mPRF) of conscious cat causes a REM sleep-like state and
state-dependent respiratory depression. Muscarinic receptors within
the mPRF have been shown to mediate this state-dependent respiratory
depression, but the specific signal transduction mechanisms remain
poorly understood. This study tested the hypothesis that the
cholinergically-induced REM sleep-like state and state-dependent
respiratory depression are mediated by guanine nucleotide binding
proteins (G proteins). Cholera toxin, pertussis toxin, 5'-guanylyl
-imidodiphosphate (GMP-PNP), and forskolin were microinjected alone
and in combination with carbachol into the mPRF of intact,
unanesthetized cat. All of the G protein-altering compounds
significantly reduced the ability of carbachol to produce the REM
sleep-like state. Pertussis toxin caused the greatest decrease in the
percent of time spent in the carbachol-evoked REM sleep-like state,
showing for the first time mediation by a pertussis toxin-sensitive
(Gi - or Go -like) G protein. Cholera toxin blocked the carbachol
-induced respiratory depression indicating mediation by a Gs -like G
protein. Forskolin significantly decreased carbachol-evoked REM
sleep. These data provide the first demonstration that adenylyl
cyclase within the mPRF contributes to the carbachol induction of REM
sleep and respiratory depression.
Received 8 July 1994; accepted in final form 9 March 1995.
APS Manuscript Number R366-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 April 1995.