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Pertussis toxin-sensitive G proteins mediate carbachol-induced REM sleep and respiratory depression
S L Shuman1, M L Capece, H A Baghdoyan
1Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Abstract:
Microinjecting cholinomimetics into the medial pontine reticular formation (mPRF) of conscious cats causes a rapid eye movement (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'-guanylylimidodiphosphate, and forskolin were microinjected alone and in combination with carbachol into the mPRF of intact unanesthetized cats. 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 G(o)-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.
Insights
Guanine nucleotide-binding proteins (G proteins) mediate rapid eye movement (REM) sleep and respiratory changes induced by cholinergic stimulation in the brainstem. This study reveals specific G protein pathways involved in REM sleep and breathing regulation.
Area of Science:
- Neuroscience
- Sleep Research
- Respiratory Physiology
Background:
- Cholinergic stimulation of the medial pontine reticular formation (mPRF) induces a REM sleep-like state and respiratory depression.
- The precise signal transduction pathways mediating these effects are not fully understood.
Purpose of the Study:
- To investigate the role of guanine nucleotide-binding proteins (G proteins) in mediating REM sleep and respiratory depression induced by cholinergic stimulation in the mPRF.
Main Methods:
- Microinjections of G protein-altering compounds (cholera toxin, pertussis toxin, 5'-guanylylimidodiphosphate, forskolin) and carbachol into the mPRF of unanesthetized cats.
- Assessment of REM sleep-like state and respiratory parameters.
Main Results:
- G protein-altering compounds significantly reduced carbachol-induced REM sleep.
- Pertussis toxin demonstrated mediation by a pertussis toxin-sensitive G protein (Gi/o-like).
- Cholera toxin blocked carbachol-induced respiratory depression, indicating mediation by a Gs-like G protein.
- Forskolin decreased carbachol-evoked REM sleep, implicating adenylyl cyclase.
Conclusions:
- G proteins are critical mediators of REM sleep and state-dependent respiratory depression induced by cholinergic stimulation in the mPRF.
- Specific G protein pathways (Gi/o and Gs) and adenylyl cyclase are involved in these processes.