Recombinant Human HCRTR1

Background

HCRTR1 is a G protein-coupled receptor that binds orexin-A, a neuropeptide involved in wakefulness, arousal, and feeding regulation. HCRTR1 is predominantly expressed in the hypothalamus, locus coeruleus, and other brain regions involved in the sleep-wake cycle, reward pathways, and energy homeostasis. It couples primarily to Gq proteins, activating phospholipase C (PLC), increasing intracellular calcium, and stimulating downstream signaling pathways such as MAPK. HCRTR1 plays a central role in maintaining wakefulness, promoting arousal, and modulating motivation and reward-seeking behavior. Dysregulation of HCRTR1 is associated with sleep disorders like narcolepsy, characterized by excessive daytime sleepiness and cataplexy, as well as addiction and obesity. Selective HCRTR1 antagonists are being developed to treat insomnia by promoting sleep onset, while agonists are explored for narcolepsy and other disorders of arousal. Its role in wakefulness, reward processing, and energy regulation makes HCRTR1 a critical therapeutic target for sleep, mood, and metabolic disorders.