Orexins and their receptors: structural aspects and role in peripheral tissues.
Orexins, also named hypocretins, were discovered in 1998 by subtractive cDNA cloning or orphan receptor technologies. Prepro-orexin is enzymatically matured into two peptides, orexin-A and orexin-B which are 33- and 28-amino-acid peptides, respectively. Two cloned orexin receptors OX1R and OX2R are serpentine G-protein-coupled receptors, both of which bind orexins and are coupled to Ca2+ mobilization. Orexins are neuropeptides present in hypothalamic neurons that project throughout the central nervous system to nuclei involved in the control of feeding, sleep-wakefulness, neuroendocrine homeostasis and autonomic regulation. The interest of investigators in orexins has focused on narcolepsy, since genetic or experimental alterations of the orexin system are associated with this sleep disorder. However, orexins are not restricted to the hypothalamus and together with their receptors they are expressed in peripheral tissues. This new multifaceted aspect of orexin biology is reviewed here in descriptions of (i) the proform, maturation and structure of orexins, (ii) the structure, signal transduction and pharmacology of orexin receptors and (iii) the expression of orexins and orexin receptors as well as their biological role in the hypothalamus-pituitary-adrenal axis, gastrointestinal tract, endocrine pancreas and other peripheral tissues.
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INSERM U410, Laboratoire de Neuroendocrinologie et Biologie Cellulaire Digestives, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, BP 416, 75870 Paris Cedex 18, France. tvoisin@bichat.inserm.fr
Rouet-Benzineb
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Reuter
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Laburthe
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D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; C000596229:HCRT protein, human; C578626:HCRTR2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011498:Protein Precursors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide