Orexins
* Please kindly note that our products and services can only be used to support research purposes (Not for clinical use).
Online Inquiry
Introduction
In 1998, the endogenous ligand of orexin (also known as hypocretin) as two orphan G protein-coupled receptors were discovered through reverse pharmacology. Orexin-A and orexin-B are two molecular forms of orexin, which derive from the same 130-aa residue precursor (proorexin-orexin). Orexin-A is a 33-aa residue peptide with two intrachain disulfide bonds, which is completely conserved in quadruped animals, Orexin-B is a linear 28-aa residue peptide. Orexin can particularly bind to orexin receptors OX1R and OX2R. OX1R and OX2R have high appetency for orexin-A, while OX2R is alternative combines by orexin-B with alike high appetency. The orexin system plays an important role in metabolism, drinking behavior, endocrine system, regulation of eating and sleep-wake cycle.
Mechanism of action
Orexin-1 receptor and orexin-2 receptor are two G protein-coupled receptors. Only when orexin binds to these two receptors can its physiological function be reflected. By deleting the proorexin-orexin or orexin-2 receptor genes or by eliminating orexin neurons, the orexin signal is damaged, leading to sleep disorders similar to narcolepsy, suggesting that the orexin system plays an important role in sleep/wakefulness accommodation. Besides, orexins are related to emotional accommodate, encouragement and pressure answer, liquid and energy stabilization. There is increasing proof show that orexin impacts the function of peripheral tissues by directly activating autonomic nervous system or by activating orexin receptor or endocrine system.
Application of Orexins
Orexins have various roles and influence many functions including autonomic regulation, endocrine function, food intake, appetite, wakefulness, and sleep. Orexins and their receptors are present in a wide range of organs outside the CNS. These molecules are involved in various physiological mechanisms. Based on the current findings, there is strong evidence supporting their functional roles in the periphery. Moreover, many studies have shown that disturbances in the expression or the levels of orexin peptides can result in pathological disorders such as late-onset obesity, impaired insulin sensitivity, hyperinsulinemia, and disturbances in gut function.
References
- Randeva, H. S., Karteris, E., Grammatopoulos, D., & Hillhouse, E. W. (2001). Expression of Orexin-A and Functional Orexin Type 2 Receptors in the Human Adult Adrenals: Implications for Adrenal Function and Energy Homeostasis. The Journal of Clinical Endocrinology & Metabolism, 86(10), 4808-4813.
- Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Yanagisawa, M. (1998). Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior. Cell, 92(4), 573-585.
