The orexin receptors are G-protein-coupled receptors (GPCRs), and consist of orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) subtypes. OX1R binds orexin-A with high affinity, but it has considerably less affinity for orexin-B. OX2R shares 64% amino acid homology with OX1R, but it is less selective, binding both orexin-A and -B with high affinity. Orexin receptors have some similarity to other neuropeptide receptors. However, neither OX1R nor OX2R has any significant affinity for neuropeptide Y, secretin, or similar peptides. OX1R and OX2R mRNA is widely expressed in the brain in a pattern similar to that of orexin nerve terminals.
Orexin receptors play vital regulatory roles in many physiological processes, especially feeding behavior, sleep-wake rhythm, reward and addiction and energy balance. Furthermore, several reports showed that orexin receptors play an improtant role in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer’s disease (AD).
Orexin A is an endogenous agonist of orexin receptors.
Orexin A, a naturally occurring neuropeptide and orexin isoform, is a specific, high-affinity agonist for G-protein-coupled receptor OX1R. Importantly, Orexin A can orchestrate diverse central and peripheral processes. Specifically, Orexin A strongly excites various brain nuclei (neurons) to affect an organism’s wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. Research shows that an absence of orexin-A appears to cause narcolepsy. Orexin A has a role in the regulation of feeding behavior. Orexin A is an effective anti-nociceptive and anti-hyperalgesic agent in mice and rats.
All in all, Orexin A is a potent anorexin receptor agonist. Orexin A can timulate feeding following central administration and play an important role in the control of sleep-wake cycle and other hypothalamic functions.