Orexin Receptor 2 (HCRTR2) Antibody

Background

HCRTR2 is a G protein-coupled receptor that binds both orexin-A and orexin-B, neuropeptides that regulate arousal, sleep-wake cycles, and energy balance. HCRTR2 is widely expressed in the hypothalamus, brainstem, and other CNS regions involved in sleep regulation, feeding behavior, and stress responses. HCRTR2 primarily couples to Gq proteins, activating phospholipase C (PLC), increasing intracellular calcium levels, and stimulating pathways such as MAPK and CREB. HCRTR2 plays a vital role in promoting wakefulness and preventing REM sleep, contributing to arousal stability and energy expenditure. Dysregulation of HCRTR2 is strongly linked to narcolepsy type 1, where loss of orexin-producing neurons leads to excessive sleepiness and disrupted sleep architecture. HCRTR2 agonists are being investigated as potential therapies for narcolepsy, while dual orexin receptor antagonists (targeting HCRTR1 and HCRTR2) are used to treat insomnia by promoting sleep onset and maintenance. HCRTR2’s critical role in wakefulness, stress, and metabolism highlights its therapeutic potential in sleep and neuropsychiatric disorders.