Orexin A (human, rat, mouse)

Product Name:Orexin A (human, rat, mouse)

CAS No:205640-90-0

Purity:95%

Molar Mass:3561.12

Chemical Formula:C152H243N47O44S4

Storage:Store at -20 degrees Celsius

Sequence:XPLPDCCRQKTCSCRLYELLHGAGNHAAGILTL

Target:OX1R and OX2R

Application:

Orexin A (human, rat, mouse) is a neuropeptide that plays a crucial role in regulating wakefulness, appetite, and energy homeostasis. It is one of two peptides derived from the prepro-orexin precursor, the other being Orexin B. Orexin A binds to both orexin receptors, OX1R and OX2R, and is involved in promoting arousal and maintaining wakefulness. Due to its significant role in the sleep-wake cycle, Orexin A is a subject of interest in research on sleep disorders such as narcolepsy, where orexin signaling is impaired. Additionally, it is studied in the context of appetite regulation, energy metabolism, and its potential link to obesity and metabolic disorders.

Current Research:

Orexin A, also known as hypocretin-1, is a 33-amino acid neuropeptide highly conserved across species, including humans, rats, and mice. Produced in the lateral hypothalamus, it plays a central role in regulating wakefulness, energy homeostasis, and various physiological processes. Orexin A interacts with two G protein-coupled receptors, orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R), exerting its diverse biological effects.

Structure
Sequence: NH₂-PEEPLNDCDCGGRTSDCRLLHSDCGRVLQRLLQANGNHAAGILTL-CONH₂
Stability: Orexin A contains two intrachain disulfide bridges that stabilize its three-dimensional structure and are critical for receptor binding.
Mechanism of Action
Orexin A binds to OX1R and OX2R, activating intracellular signaling pathways, including calcium mobilization, adenylyl cyclase stimulation, and MAPK phosphorylation. These pathways regulate neuronal activity and coordinate physiological responses related to arousal and metabolism.

Physiological Functions
Sleep-Wake Regulation:

Orexin A promotes wakefulness and prevents the onset of REM sleep. Dysfunction in the orexin system is implicated in narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy.
Energy Homeostasis:

Orexin A modulates feeding behavior and energy expenditure by influencing metabolic processes and autonomic nervous system activity.
Reward and Motivation:

Orexin A is involved in reward-seeking behaviors, including responses to food, drugs, and other reinforcing stimuli, highlighting its role in addiction and motivation.
Stress Response:

The orexin system interacts with stress pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, to coordinate adaptive responses.
Cardiovascular Regulation:

Orexin A influences heart rate and blood pressure through its effects on autonomic nervous system function.
Research Applications
Sleep Disorders:

Orexin A is used to study mechanisms of narcolepsy and other sleep-related conditions.
It serves as a target for therapeutic interventions aimed at improving wakefulness or promoting sleep.
Obesity and Metabolism:

Research investigates orexin A's role in energy balance, offering insights into potential treatments for obesity and metabolic syndrome.
Addiction:

Orexin A is used to study its influence on reward circuitry and its potential as a target for addiction therapies.
Neurodegenerative Diseases:

Its involvement in neuronal excitability and metabolism makes orexin A a subject of interest in diseases like Alzheimer’s and Parkinson’s.
Cardiovascular Research:

Studies explore its role in regulating autonomic responses and potential therapeutic applications in hypertension.
Handling and Storage
Form: Typically supplied as a lyophilized powder.
Storage: Store at -20°C in a desiccated environment to preserve stability.
Reconstitution: Reconstitute in sterile water or buffer suitable for experimental use.
Conclusion
Orexin A is a multifunctional neuropeptide with wide-ranging effects on sleep, metabolism, and stress regulation. Its conservation across species and critical physiological roles make it a key target in research on sleep disorders, metabolic regulation, addiction, and neurodegeneration.

Reference:

Nakabayashi, M., Suzuki, T., Takahashi, K., Totsune, K., Muramatsu, Y., Kaneko, C., ... & Sasano, H. (2003). Orexin-A expression in human peripheral tissues. Molecular and cellular endocrinology, 205(1-2), 43-50.