Carbachol stimulates [35S]guanylyl 5'-(gamma-thio)-triphosphate binding in rapid eye movement sleep-related brainstem nuclei of rat.
Carbachol enhances rapid eye movement (REM) sleep when microinjected into the pontine reticular formation of the cat and rat. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs). The present study used in vitro autoradiography of carbachol-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding to test the hypothesis that carbachol activates mAChRs to induce stimulation of G-proteins in brainstem nuclei contributing to REM sleep generation. The results demonstrate a heterogeneous increase in carbachol-stimulated G-protein activation across rat brainstem. Binding of [35S]GTPgammaS in the presence of carbachol, compared with basal binding, was significantly increased in the laterodorsal tegmental nucleus (75.7%), caudal pontine reticular nucleus (68.9%), oral pontine reticular nucleus (64.5%), pedunculopontine tegmental nucleus (55.7%), and dorsal raphe nucleus (54.0%) but not in the nucleus locus coeruleus. The activation of G-proteins by carbachol was concentration-dependent and antagonized by atropine, demonstrating that G-proteins were activated via mAChR stimulation. The results provide the first direct measures of mAChR-activated G-proteins in brainstem nuclei known to contribute to REM sleep generation.
Capece
M L
ML
Department of Anesthesia, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.
Baghdoyan
H A
HA
Lydic
R
R
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001345:Autoradiography; D002217:Carbachol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology*; D013462:Sulfur Radioisotopes
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001285:Atropine; D002217:Carbachol; D019204:GTP-Binding Proteins