OREXINS AND OREXIN RECEPTORS - A FAMILY OF HYPOTHALAMIC NEUROPEPTIDESAND G-PROTEIN-COUPLED RECEPTORS THAT REGULATE FEEDING-BEHAVIOR

The hypothalamus plays a central role in the integrated control of fee ding and energy homeostasis. We have identified two novel neuropeptide s, both derived from the same precursor by proteolytic processing, tha t bind and activate two closely related (previously) orphan G protein- coupled receptors. These peptides, termed orexin-A and -B, have no sig nificant structural similarities to known families of regulatory pepti des. prepro-orexin mRNA and immunoreactive orexin-A are localized in n eurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated u pon fasting, suggesting a physiological role for the peptides as media tors in the central feedback mechanism that regulates feeding behavior .