Orexins

Literature References: Neuropeptides produced in the hypothalamus that are involved in the regulation of feeding behavior and the sleep-wake cycle. Name derived from the Greek word, orexis, meaning appetite. Fasting increases orexin production; administration of exogenous orexin stimulates feeding. Also implicated in the pathophysiology of narcolepsy. Two forms are known (orexins A and B); both are derived from the same precursor protein. Two orexin receptors (OX1R and OX2R) have been identified in mammalian brain. OX1R binds only orexin A while OX2R is a non-selective receptor for both A and B. Identification of hypothalamus-specific mRNA that encodes the orexin precursor: L. De Lecea et al., Proc. Natl. Acad. Sci. USA 95, 322 (1998). Purification and biological activity of orexins: T. Sakurai et al., Cell 92, 573 (1998). Immunohistochemical localization in rat brain: Y. Date et al., Proc. Natl. Acad. Sci. USA 96, 748 (1999). Association of canine narcolepsy with OX2R defect: L. Lin et al., Cell 98, 365 (1999); of sleep disorder in orexin knockout mice: R. M. Chemelli et al., ibid. 437. Clinical determn of orexin deficiency in CSF of narcoleptic patients: S. Nishino et al., Lancet 355, 39 (2000). Review of structure, tissue distribution and role in feeding behavior: T. Sakurai, Regul. Pept. 85, 25-30 (1999). Review of role in narcolepsy and potential therapeutic application: J. M. Siegel, Cell 98, 409-412 (1999).