Involvement of orexins/hypocretins in multiple physiological functions

Abstract

Orexins (orexin-A and orexin-B)/hipocretins (hypocretin-1 and hypocretin-2) are novel neuropetides discovered in 1998. Orexin-producing neurons are exclusively distributed in the lateral hypothalamic area (LHA), the posterior hypothalamic area and the perifornical nucleus in rats. The LHA is known to be a feeding center in the hypothalamus. Central administration of orexins stimulated feeding in rats and mice. Therefore, orexins are recognized as potent orexigenic peptides. In a positional cloning study, genetically narcoleptic dogs had a deletion of the orexin receptor 2 gene, resulting in a truncated, nonfunctional receptor. Orexin knockout mice were found to exhibit narcoleptic behavior. In human narcoleptic patients, hypocretin-1 in cerebrospinal fluid was undetectable in almost all patients with narcolepsy. Although the physiological role of feeding seems to be independent of sleep, it is very interesting that orexins may be common bioactive substances that are involved in regulating feeding and sleep. The discovery of orexins may contribute to clarify the pathogenesis of disorders in feeding and sleep and to develop drugs for those disorders.