Introduction of HCRTR1
Orexin receptor type 1 (Ox1R or OX1), alternatively known as HCRTR1 (Hypocretin receptor type 1), is a membrane protein which in human is encoded by HCRTR1 gene. It is recognized as a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus. HCRTR1 shares 64% identity with hypocretin receptor type 2 (HCRTR2), which is also called orexin receptor type 2 (Ox2R). This protein acts as a moderately selective excitatory receptor for orexin-A, and with a lower affinity for orexin-B neuropeptide.
|Basic Information ofHCRTR1|
|Protein Name||Hypocretin receptor type 1|
|Organism||Homo sapiens (Human)|
Function of HCRTR1 Membrane Protein
HCRTR1 selectively binds the orexin-A neuropeptide and is involved in the regulation of feeding behaviour. Normally, the activation of HCRTR1 induces cellular calcium transients in receptor-transfected cells and native receptor-expressing cells. This occurs by the increase of intracellular inositol triphosphate and subsequent release of calcium from intracellular stores. HCRTR1 is involved in multiple phospholipase activities including phospholipases C and D. HCRTR1 has also been suggested to being linked to calcium influx via the canonical transient receptor potential channel TRPC3. Other reports also demonstrated that the activation of HCRTR1 can lead to stimulation of cAMP production. Activation of HCRTR1 induces apoptosis in colon cancer cells or HCRTR1-transfected cells through Gq protein but independently of classical Gαq activation of phospholipase C and calcium pathway. Besides, a number of small-molecule HCRTR1 antagonists have been described due to their potential interest as a novel therapy for the treatment of insomnia.
Fig.1 Structure of HCRTR1 membrane protein.
Application of HCRTR1 Membrane Protein in Literature
The results of this article suggested that rostral ventromedial medulla orexin-A receptors were involved in pulpal nociceptive modulation and improvement of learning and memory deficits induced by intradental application of capsaicin.
This study was carried out to investigate the effects of intrathecal administration of orexin-1 receptor antagonist (SB-334867) in the spinal antinociception induced by intra-LH administration of carbachol (cholinergic receptor agonist) in both early and late phases of pain-related behaviors in the formalin test.
Authors in this group indicated that vagus nerve stimulation promoted the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OX1R expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.
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. They found that when orexin 1 and 2 receptors in the BLA were blocked after LTP induction, there were no differences between the DMSO and treatment groups.
Findings of this articlesupportedthatOX1rs in the CA1 region of the hippocampus were involved in the expression of morphine CPP (conditioned place preference). Moreover, blockade of OX1rs could facilitate extinction and may extinguish the ability of drug-related cues. It seemed that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behaviors.
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