Orexin

links: Neuropeptide reference: 4-21-2021

Orexin (Hypocretin) #

• There’s 2 proteins of the Hcrt gene: orexin-A and orexin-B. The gene encodes prepro-orexin.
  • A has equal affinity to OX1 and OX2. B has 5x more affinity for OX2.
  • 2 receptors; OX1R/HCRTR1 and OX2R/HCRTR2.
  • (OXA binds to OX1/OX2 with equal affinity, while OXB binds to OX2 with 5x more affinity than OX1.)
• Stimulating; regulates arousal, wakefulness, and appetite.
• Sensitizes NMDA.
• High during the day, and low at night; reduction promotes deep sleep.
  • Can decrease it with alkalinity, GABA, Adenosine, dopamine, and 5-HT1 agonists.
• Increased by stress/Corticotrophin-releasing hormone, Hypothyroidism, Noradrenaline, and [[Glutamate]
• ] Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response
• Stimulation of orexin/hypocretin neurones by thyrotropin-releasing hormone
• Orexin Receptor Multimerization versus Functional Interactions: Neuropharmacological Implications for Opioid and Cannabinoid Signalling and Pharmacogenetics
  • OX1/OX2 (GPCRs) receptors heteromerize with CB1 and Opioid Receptors.