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The orexins (hypocretins) are a newly discovered family of neuropeptides which play a role in regulating feeding and wakefulness. The family currently consists of two members; orexin A and orexin B (33- and 28-residues respectively), which are produced from a common precursor prepro-orexin (130 amino acids). Cell bodies of orexin-containing neurons are largely confined to the lateral hypothalamus, an area classically linked to feeding stimulation. Intracerebroventricular injections of orexin A and orexin B stimulate feeding in a dose-related manner, with orexin A being significantly more effective than orexin B. Orexins are also strongly linked to the regulation of sleep-activity cycles, which may restrict the use of orexin ligands in the treatment of obesity. The orexins activate two G-protein-coupled receptors (OX1 and OX2) also found predominantly in the hypothalamus. Orexin A is the selective endogenous agonist for OX1 and blocking this receptor modulates food and water intake.
Tocris offers the following scientific literature for Orexin Receptors to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Written by Sonia Tucci, Lynsay Kobelis and Tim Kirkham, this review provides a synopsis of the increasing number of peptides that have been implicated in appetite regulation and energy homeostasis; putative roles of the major peptides are outlined and compounds available from Tocris are listed.
|Receptor Subtype||OX1 Receptors||OX2 Receptors|
|Transduction Mechanism||↑ PLC → ↑ Ca2+ influx||↑ PLC → ↑ Ca2+ influx|
|Primary Locations||Ventromedial hypothalamus, locus coeruleus, median raphe, hippocampus, tenia tecta||Cerebral cortex (layers IV-VI), medial hypothalamus, paraventricular hypothalamus, nucleus accumbens, subthalamic and paraventricular thalamus, anterior pretectal nucleus|
|Likely Physiological Roles||Sleep-wakefulness, energy homeostasis||Sleep-wakefulness|
|Key Compounds||Ki Values (nM)|
|Orexin A (human, rat, mouse) (1455)||20||38|
|Orexin B (human) (1456)||420||36|
|SB 334867 (1960)||7.2*||< 5*|
|SB 408124 (1963)||21.7†||1405†|
|[Ala11,D-Leu15-Orexin B (2142)||52‡||0.13‡|
* pKb value, † Kb value, ‡ EC50 value
Smart et al (1999) Cahracterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell line using FLIPR. Br.J.Pharmacol. 128 1. Sutcliffe and de Lecea (2000) The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding. J.Neurosci. Res. 62 161. Smart (1999) Orexins: a new family of neuropeptides. Br.J.Anaesth. 83 695. Smart et al (2001) SB-334867-A: the first selective orexin-1 receptor antagonist. Br.J.Pharmacol. 132 1179. Asahi et al (2003) Development of an Orexin-2 receptor selective agonist [Ala11,D-Leu15orexin -B. Bioorg.Med.Chem.Letts. 13 111. Langmead et al (2004) Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor. Br.J.Pharmacol. 141 340.