Pertussis toxin-sensitive G proteins mediate carbachol-induced REM sleep and respiratory depression.
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.
Shuman
S L
SL
Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Capece
M L
ML
Baghdoyan
H A
HA
Lydic
R
R
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002415:Cats; D019204:GTP-Binding Proteins / Q000502:physiology*; D008297:Male; D008845:Microinjections; D037342:Pertussis Toxin; D011149:Pons / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012154:Reticular Formation / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000502:physiology*; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins