![]() They found that the orexin peptides activated the cells expressing the orexin receptors and went on to find orexin peptide expression specifically in the hypothalamus. To this end, they used transgenic cell lines that expressed individual orphan receptors and then exposed them to different potential ligands. On the other hand, Sakurai and colleagues were studying the orexin system as orphan receptors. A majority of these projections reached the limbic system and structures associated with it (including the amygdala, septum, and basal forebrain area). ![]() These cells were first thought to reside and work only within the lateral hypothalamus area, but immunocytochemistry techniques revealed the various projections this area truly had to other parts of the brain. Neurotransmitters found in this area were oddly similar to the gut hormone, secretin, a member of the incretin family, so they named hypocretin to stand for a hypothalamic member of the incretin family. They cloned this DNA and studied it using electron microscopy. They extracted selective DNA found in the lateral hypothalamus. In 1996, scientists from the Scripps Research Institute reported the discovery of several genes in the rat brain, including one they dubbed "clone 35." Their work showed that clone 35 expression was limited to the lateral hypothalamus. One team was interested in finding new genes that were expressed in the hypothalamus. The two groups also took different approaches towards their discovery. Masashi Yanagisawa and Emmanuel Mignot were awarded the Breakthrough Prize in 2022 for this discovery. In their 1998 paper describing these neuropeptides, they also reported discovery of two orexin receptors, dubbed OX 1R and OX 2R. Luis de Lecea, Thomas Kilduff, and colleagues reported the discovery of the hypocretin system at the same time as Takeshi Sakurai from Masashi Yanagisawa's lab at the University of Texas Southwestern Medical Center at Dallas reported the discovery of the orexins to reflect the orexigenic (appetite-stimulating) activity of these peptides. In 1998, reports of the discovery of orexin/hypocretin were published nearly simultaneously. There is considerable similarity between the orexin system in the rat brain and that in the human brain. Officially, hypocretin ( HCRT) is used to refer to the genes and transcripts, while orexin is used to refer to the encoded peptides. One group named it orexin, from orexis, meaning "appetite" in Greek the other group named it hypocretin, because it is produced in the hypothalamus and bears a weak resemblance to secretin, another peptide. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. There are two types of orexin peptide and two types of orexin receptor. ![]() They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it. ![]() Orexin ( / ɒ ˈ r ɛ k s ɪ n/), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. Solution phase NMR structure of orexin B based on the PDB coordinates 1CQ0. ![]()
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