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Cell Signal. 2013 Dec;25(12):2413-23. doi: 10.1016/j.cellsig.2013.07.025. Epub 2013 Aug 1.

Orexin receptors: multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers and other physiological disorders.

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Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address:


The orexin peptides (orexin A, orexin B) and their receptors (orexin receptor type 1, orexin receptor type 2) are involved in multiple physiological processes such as the regulation of sleep/wakefulness state, energy homeostasis and reward seeking. A result of this has been the development of small-molecule orexin receptor antagonists as novel therapies for the treatment of insomnia and drug addiction. Increased levels of signaling via the orexin peptide/receptor system may protect against obesity, while somewhat unexpectedly, orexins acting at orexin receptors induce dramatic apoptosis resulting in the significant reduction of cell growth in various cancer cell lines. Meanwhile, the orexin peptide/receptor system is also involved in cardiovascular modulation, neuroendocrine and reproduction regulation. This review summarizes the latest developments in deciphering the biology of orexin signaling as well as efforts to manipulate orexin signaling pharmacologically.


5-HT; 5-hydroxytryptamine; AC; Addiction; BAT; BMP; BST; CB1R; CNS; CREB; Cancers; DRN; ERK; Energy homeostasis; FAA; G protein coupled receptors; GABA; GH; GPCR; HA; HIF1; HPA; HPG; ICV; ITIM; ITSM; LH; MAPK; NAc; NPY; NSCC; OX1R; OX2R; Orexin receptors; Orexins; OxA; OxB; PH; PKA; PKC; PLC; REM; RN; RVM; SN; Sleep/wakefulness state; Smad; TGF-β; TMN; VTA; adenylyl cyclase; bed nucleus of the stria terminalis; bone morphogenetic protein; brown adipose tissue; cAMP-response element binding protein; cannabinoid receptor type 1; central nervous system; dorsal raphe nucleus; drosophila mothers against decapentaplegic protein; extracellular signal regulated kinase; food anticipatory activity; gamma-aminobutyric acid; growth hormone; histamine; hypothalamic–pituitary–adrenal; hypothalamic–pituitary–gonadal; hypoxia-inducible factor-1; immunoreceptor tyrosine-based inhibitory motif; immunoreceptor tyrosine-based switch motif; intracerebroventricular; lateral hypothalamus; mitogen-activated protein kinase; neuropeptide Y; nonselective cationic conductance; nucleus accumbens; orexin A; orexin B; orexin receptor type 1; orexin receptor type 2; pCREB; phospholipase C; phosphorylated cAMP response element-binding protein; posterior hypothalamus; protein kinase A; protein kinase C; rRPa; raphe nuclei; rapid eye movement; rostral raphe pallidus; rostral ventromedial medulla; substantia nigra; transforming growth factor-β; tuberomammillary nucleus; ventral tegmental area

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