Orexin Receptor Type 1 and Type 2 (OX1R/OX2R)

Orexin receptors, also known as hypocretin receptors, are G protein–coupled receptors (GPCRs) that mediate the physiological effects of the neuropeptides orexin-A and orexin-B. There are two main subtypes: Orexin receptor type 1 (OX1R, HCRTR1) and Orexin receptor type 2 (OX2R, HCRTR2). They play critical roles in regulating arousal, wakefulness, appetite/feeding behavior, and energy homeostasis. OX1R is more involved in reward-seeking behavior and arousal, while OX2R plays a dominant role in sleep-wake regulation. Several antagonists targeting these receptors have been developed for treating sleep disorders such as insomnia. Both receptors activate Gq proteins leading to increased intracellular calcium levels and downstream signaling including activation of ERK pathways.

Other names

HCRTR1/HCRTR2Orexin receptor type I and IIHypocretin receptor type 1 and 2OXR1/OXR2

GPCR activation via orexin-A or orexin-B binding; Gq protein activation, increase of intracellular calcium levels; ERK pathway activation; Antagonists block orexin binding and subsequent activation.