Orexin neurons receptors

Yamanaka, A., Tsujino, N., Funahashi, H. el al. (2002). Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem. Biophys. Res. Commun. 290, 1237-45. 

Significantly, orexin/ataxin-3 mice respond to intracerebroventricular injection of orexin-A with increased wakefulness and suppression of REM sleep and cataplexy. This pharmacological reversal indicated that orexin receptors remain functional in the absence of orexin neurons, and that these narcoleptic mice can respond to orexin agonists, a finding with significant therapeutic implications (Mieda et al., 2004b). 

Finnegan TF, Chen SR, Pan HL (2006) Mu opioid receptor activation inhibits GABAergic inputs to basolateral amygdala neurons through Kvl.1/1.2 channels. J Neurophysiol 95 2032-41 Fu LY, Acuna-Goycolea C, van den Pol (2004) Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms tonic depression of the hypothalamic arousal system. J Neurosd 24 8741-51... 

In the context of the present chapter, it is of special interest that orexin/hypocretin-containing hypothalamic neurons innervate in the ventral midbrain tegmentum the VTA and the SNc with a dense plexus of terminal fibers, whereas the SNr is substantially spared (Fig. 15). Consistently with this pattern of orexin/hypocretin innervation, in the rat orexin 1 and orexin 2 receptor mRNAs are very dense in both the VTA and the SNc, whereas no orexin receptor expression has been detected in the SNr (Marcus et al., 2001). 

Hakansson M, de Lecea L. Sutcliffe. TG. Yanagisawa M, Meister B. Leptin receptor- and STAT3-immunore-activities in hypocretin/orexin neurones of the lateral hypothalamus. J Neuroendocrinol 1999 11 653-663. 

Extrahypothalamic OX-B-like immunoreactivity, reminiscent to that of CRF, has been described in clustered GABAergic neuronal populations, in the lateral division of central nucleus ofthe amygdala, the bednucleus of the stria terminalis, and in the hippocampus. Moreover, ectopic expression of preproorexin mRNA in the gut, ependymal cells, neuroblastomas, and of orexin receptors in adrenal gland, cancer and hematopietic stem cells suggests yet unexplored roles of orexins as paracrine factors controlling blood-brain barrier, and tumor or stem cell function. 

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, may be caused by the lack of hypocretin mRNA and peptides in humans (Peyron et al., 2000) or a disruption of the hypocretin receptor 2 or its ligand in dogs and mice (Lin et al., 1999 Chemelli et al., 1999). Hypocretin-containing neurons are located exclusively in the dorsomedial, lateral, and perifornical hypothalamic areas (Peyron et al., 1998). Two hypocretin sequences, Hcrt-1 (orexin-A) and Hcrt-2 (orexin-B), are generated from a single preprohypocretin (De Lecea et al., 1998 Peyron et al, 1998 Sakurai et al, 1998). Axons from these neurons are found in the hypothalamus, locus coeruleus (LC), raphe nuclei, tuberomamillary nucleus, midline thalamus, all levels of spinal cord, sympathetic and parasympathetic centers, and many other brain regions... 

Backberg, M., Hervieu, G., Wilson, S. Meister, B. (2002). Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus focus on orexin targets involved in control of food and water intake. Eur. J. Neurosci. 

Willie, J. T., Chemelli, R. M., Sinton, C. M. et at (2003). Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron, 38, 715-30. 

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