The hypocretins and sleep.
The hypocretins (also called the orexins) are two neuropeptides derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein coupled receptors for the hypocretins have been identified, and these show different distributions within the central nervous system and differential affinities for the two hypocretins. Hypocretin fibers project throughout the brain, including several areas implicated in regulation of the sleep/wakefulness cycle. Central administration of synthetic hypocretin-1 affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement sleep. Most human patients with narcolepsy have greatly reduced levels of hypocretin peptides in their cerebral spinal fluid and no or barely detectable hypocretin-containing neurons in their hypothalamus. Multiple lines of evidence suggest that the hypocretinergic system integrates homeostatic, metabolic and limbic information and provides a coherent output that results in stability of the states of vigilance.
de Lecea
Luis
L
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. llecea@scripps.edu
Sutcliffe
J Gregor
JG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014018:Tissue Distribution; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D006728:Hormones; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled