Introduction of HCRTR2
Orexin receptor type 2 (Ox2R or OX2), alternatively known as HCRTR2 (Hypocretin receptor type 2), is a membrane protein which in human is encoded by the HCRTR2 gene. It is recognized as a G-protein coupled receptor that is exclusively expressed in the brain, especially in histaminergic cells of the tuberomammillary nucleus. HCRTR2 shares 64% identity with hypocretin receptor type 1 (HCRTR1), which is also called orexin receptor type 1 (Ox1R). This receptor has a high-affinity for both orexin-A and orexin B neuropeptides.
|Basic Information ofHCRTR2|
|Protein Name||Hypocretin receptor type 2|
|Organism||Homo sapiens (Human)|
Function of HCRTR2 Membrane Protein
Orexin receptors is capable of coupling to multiple G proteins. Experimental studies show that HCRTR2 in human adrenal cortex activate Gi, Gs, and Gq proteins. HCRTR2 appears to have similar affinity for orexin-A and orexin-B in binding assays and biological response such as stimulation of apoptosis. HCRTR2 triggers an increase in cytoplasmic Ca2+ levels in response to orexin-A binding. HCRTR2 is also reported to be linked to the risk of cluster headache (CH). HCRTR2 is involved in a wide range of other functions such as addiction, stress response and metabolic regulation. HCRTR2-deficient animals exhibit a phenotype remarkably similar to the human sleep disorders, narcolepsy, which is characterized by sleep/wakefulness fragmentation. Accordingly, HCRTR2 stimulation is supposed to have important pharmacological uses, most obviously in symptomatic treatment of narcolepsy, and maybe other sleep and vigilance disorders. HCRTR2 stimulation is also able to induce programmed cell death in different types of cancer cells, and thus might provide a novel way of cancer treatment.
Fig.1 Structure of HCRTR2 membrane protein.
Application of HCRTR2 Membrane Protein in Literature
Authors in this group focused on the structures of human orexin 2 receptor in complex with the subtype-selective antagonist EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) at 2.30-Å and 1.96-Å resolution. The results should facilitate the development of antagonists for orexin receptors.
This study was carried out to investigate the central and/or local effects on gonadal functions. The findings provide the first definite evidence for the immunohistochemical localization of OXB and OX2R in the principal cells of rat epididymis.
This article focuses on investigating the effects of orexin 1 and 2 receptor antagonism in the basolateral amygdala (BLA) on long-term potentiation (LTP) of dentate gyrus (DG) granular cells. Theyfoundthatwhen orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups.
Authors in this group indicated that in a psychological stress model, genetic or pharmacological inhibition of OX2R markedly attenuated stress-induced ACTH secretion, as a separately mediated effect from the NREM sleep induction of OX2R antagonism.
This article reported the direct excitatory effect of orexin on an inhibitory motor structure, the Gi. This modulation may be integrated into the role of orexin in central motor control.
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