Hypocretin-1 activates G proteins in arousal-related brainstem nuclei of rat.
The hypocretin (hcrt) ligand-receptor system contributes to the maintenance of wakefulness. Hypocretin receptors are coupled to guanine nucleotide binding (G) proteins and the present study tested the hypothesis that hcrt-1 would activate G proteins in rat brainstem nuclei known to regulate arousal states. In vitro [35S]GTPgammaS autoradiography was performed using coronal brain stem sections from six rats. Hcrt-1 (200 nM) significantly increased [35S]GTPgammaS binding over basal levels in locus coeruleus (24%), dorsal raphe nucleus (12%), pontine reticular nucleus, oral part (28%), and pontine reticular nucleus, caudal part (40%). This is the first study to quantify and localize hcrt-1-induced G protein activation in specific brain stem nuclei. The finding that hcrt-1 stimulated [35S]GTPgammaS binding suggests that some hcrt receptors in pontine brain stem couple to inhibitory G proteins.
Bernard
René
R
Department of Pharmacology, University of Michigan, 7433 Medical Sciences Building 1, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
Lydic
Ralph
R
Baghdoyan
Helen A
HA
D000818:Animals; D001143:Arousal / Q000502:physiology*; D001933:Brain Stem / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins