orexin

Meaning: Orexin (also called hypocretin) is a pair of neuropeptides, orexin-A and orexin-B, made by neurons in the lateral hypothalamus. They bind G protein-coupled receptors (OX1R and OX2R) on neurons across the brain, which promotes wakefulness and arousal. Orexin also stimulates appetite; the name comes from the Greek word for appetite. Orexin neurons are active during wakefulness, and ghrelin excites them while leptin inhibits them.

On the MCAT: Expect a passage on animals or patients that lack orexin neurons or receptors, asking you to predict unstable sleep-wake states, as in narcolepsy, with sudden shifts into sleep during the day. A receptor antagonist would be predicted to promote sleep. Orexin also appears in hypothalamus questions: the lateral hypothalamus drives hunger and arousal, while the ventromedial hypothalamus is tied to satiety. Because the receptors are GPCRs, you may also be asked to trace the signal through G proteins and second messengers.

Common confusion: Students mix orexin up with melatonin or with an appetite suppressant. Melatonin comes from the pineal gland and rises in darkness, whereas orexin promotes waking. The name derives from orexis, meaning appetite, so orexin increases hunger rather than reducing it. Loss of orexin signaling causes excessive sleepiness and sleep-wake instability, not insomnia.