Activation of Hypocretin Neurons and Sleep

The hypocretins (hcrt-1 and hcrt-2), also called orexins (OX-A and OX-B), are neuropeptides first described because of their restricted expression in a subset of hypothalamic neurons (de Lecea et al., 1998). The hypocretin precursor gives raise to two peptides named hypocretin-1 and hypocretin-2, after their sequence similarity to secretin and the prominent expression of preprohypocretin mRNA in the hypothalamus. Independently, Sakurai et al. (1998) identified identical peptides from brain extracts through their ability to bind and activate orphan G-protein coupled receptors. These authors also showed that when injected into the brain ventricles, the peptides stimulate food intake, thus they named them orexins, from the Greek word orexis (appetite).