Journal
NEUROREPORT
Volume 13, Issue 4, Pages 447-450Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00001756-200203250-00017
Keywords
dorsal raphe nucleus; hypocretin receptors; in vitro [S-35]GTP gamma S autoradiography; locus coeruleus; narcolepsy; orexin; pontine reticular formation; REM sleep; wakefulness
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Funding
- NHLBI NIH HHS [HL40881, HL65272, HL57120] Funding Source: Medline
- NIMH NIH HHS [MH45361] Funding Source: Medline
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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-I would activate G proteins in rat brainstem nuclei known to regulate arousal states. In vitro [S-35]GTPgammaS autoradiography was performed using coronal brain stem sections from six rats. Hcrt-1 (200 nM) significantly increased [S-35]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-l-induced G protein activation in 3 specific brain stem nuclei. The finding that hcrt-I stimulated [S-35]GTPgammaS binding suggests that some hcrt receptors in pontine brain stem couple to inhibitory G proteins.
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