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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

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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.

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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].

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