Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Feb;9(1):39-45.
doi: 10.1016/j.coph.2008.12.018.

The brain hypocretins and their receptors: mediators of allostatic arousal

Matthew E Carter  1 , Jana Schaich Borg, Luis de Lecea
Affiliations
Review

The brain hypocretins and their receptors: mediators of allostatic arousal

Matthew E Carter et al. Curr Opin Pharmacol. 2009 Feb.

Abstract

The hypocretins (abbreviated 'Hcrts' - also called 'orexins') are two neuropeptides secreted exclusively by a small population of neurons in the lateral hypothalamus. These peptides bind to two receptors located throughout the brain in nuclei associated with diverse cognitive and physiological functions. Initially, the brain Hcrt system was found to have a major role in the regulation of sleep/wake transitions. More recent studies indicate Hcrts may play a role in other physiological functions, including food intake, addiction, and stress. Taken together, these studies suggest a general role for Hcrts in mediating arousal, especially when an organism must respond to unexpected stressors and challenges in the environment.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Afferent projections of hypocretin neurons and expression of hypocretin receptors
Hcrt neurons project widely throughout the brain, including the LC, TMN, VTA, dorsal raphe nuclei, other hypothalamic nuclei, and the cortex.
Figure 2
Figure 2. The brain hypocretins and their receptors
Hcrt1 and Hcrt2 are both spliced from the same genetic precursor, Preprohypocretin. Hcrt1 binds with high affinity to both Hcrt receptors, while Hcrt2 only binds with high affinity to Hcrtr-2. Hcrt receptors are differentially expressed throughout the brain, with Hcrtr-1 expressed in the LC and LDT/PPT, and Hcrtr-2 expressed in the TMN. Modified from [14].
See this image and copyright information in PMC

References

    1. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98:365–376. - PubMed
    1. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98:437–451. These studies were the first to indicate that dyregulation of the Hcrt system is sufficient to cause narcolepsy. These seminal publications greatly increased our understanding of the cause of narcolepsy and sleep disorders and also discovered a crucial role for the Hcrts in the maintenance of wakefulness and arousal. - PubMed
    1. Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron. 2001;30:345–354. - PubMed
    1. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000;355:39–40. - PubMed
    1. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, Cornford M, Siegel JM. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27:469–474. - PMC - PubMed

Publication types