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 [S]GTPγS autoradiography was performed using coronal brain stem sections from six rats. Hcrt-1 (200 nM) significantly increased [S]GTPγS 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 [S]GTPγS binding suggests that some hcrt receptors in pontine brain stem couple to inhibitory G proteins.