Orexin GPCR Assays
Background of Orexin Receptors
The orexins, also known as hypocretins, are a family of neuropeptides that play important roles in the regulation of feeding and wakefulness. The orexin receptors are G-protein-coupled receptors that bind the neuropeptide orexin, thereby activating different downstream signaling pathways and exerting a variety of physiological functions. There are several orexin receptor antagonists in development for the treatment of sleep disorders.
Fig.1 Schematic summary of signaling pathways mediated by the orexin/receptor system. (Wang, 2018)
Distribution and Functions of Orexin Receptors
The expression of orexin receptors can be detected in areas of the central nervous system, such as the pedunculopontine tegmental nucleus (PPT), ventral tegmental area (VTA), and laterodorsal tegmental nucleus (LDT). In particular, the OX1 receptor is preferentially expressed in the locus coeruleus (LC), while the OX2 receptor is mainly distributed in the nodular papillary nucleus (TMN).
Subtypes and Mechanisms of Orexin Receptors
There are two variants of the orexin receptor have been identified, including the OX1 receptor and the OX2 receptor, encoded by two genes, HCRTR1 and HCRTR2, respectively. The OX1 receptor binds orexin-A with high affinity, while the OX2 receptor binds both orexin-A and orexin-B with high affinity.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| OX1 receptor | HCRTR1 |
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| OX2 receptor | HCRTR2 |
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Assay List of Orexin Receptors
Creative Biolabs can provide a range of assays of orexin receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title |
Effects of orexin receptor antagonism on human sleep architecture: a systematic review |
| Journal |
Sleep Medicine Reviews |
| Published | 2020 |
| Abstract |
Orexin receptor antagonists have been used for hypnosis, but the mechanism by which they affect human sleep has not been clarified. This article evaluates how these compounds affect sleep in humans by systematically searching PubMed, Embase, and Cochrane for controlled trials. Of these, dual orexin receptor antagonists (DORAs) were used in 15 studies, and selective orexin receptor 2 antagonists (2-SORAs) were used in three additional studies. The results showed that DORA increased total sleep time mainly by promoting rapid eye movement (REM) sleep but did not affect non-REM sleep. For 2-SORAs, no clear conclusions have been drawn to show their impact on human sleep architecture. In the future, further studies of 2-SORAs are needed to determine their impact and, on this basis, to compare with DORAs. |
| Result |
This literature systematically verified that DORA promotes the increase of total sleep time (TST) mainly by promoting REM sleep. For example, increasing the TST has a clear advantage for non-comorbid insomnia. In contrast, subjects characterized by REM sleep deprivation may particularly benefit from this feature of DORA. If preclinical and human data suggest that 2-SORAs may increase REM and NREM sleep are confirmed in future studies, 2-SORAs may offer an alternative to DORAs in populations targeting increased REM and NREM sleep.
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Fig.2 Reports of dual orexin receptor antagonist (DORA) effectiveness in healthy control and insomnia samples. (Clark, 2020)
References
- Wang, C.; et al. The orexin/receptor system: molecular mechanism and therapeutic potential for neurological diseases. Frontiers in molecular neuroscience, 2018: 220.
- Clark, J.W.; et al. Effects of orexin receptor antagonism on human sleep architecture: a systematic review. Sleep Medicine Reviews. 2020, 53: 101332.
