Abstract
Orexin-A and -B are two peptides derived by proteolytic cleavage from a 130-amino acid precursor, prepro-orexin, which were recently isolated from the rat hypothalamus. Orexin-A is fully conserved across mammalian species, whilst rat and human orexin-B differ by two amino acids. These peptides bind to two Gq-coupled receptors, termed orexin-1 and orexin-2. The receptors are 64% homologous and highly conserved across species. Orexin-A is equipotent at orexin-1 and orexin-2 receptors, whilst orexin-B displays moderate (approximately 10 fold) selectivity for orexin-2 receptors. The distribution and pharmacology of the orexin peptides and their receptors indicate that they play a role in various regulatory systems including energy homeostasis and the regulation of feeding, the evidence for which is reviewed here.
MeSH terms
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Animals
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Benzoxazoles / pharmacology
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Body Weight / drug effects
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Body Weight / physiology
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Carrier Proteins / pharmacology
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Carrier Proteins / physiology*
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Eating / drug effects
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Eating / physiology
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Humans
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Intracellular Signaling Peptides and Proteins*
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Naphthyridines
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Neuropeptides / pharmacology
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Neuropeptides / physiology*
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Obesity / drug therapy
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Obesity / physiopathology*
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide / agonists
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Receptors, Neuropeptide / antagonists & inhibitors
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Receptors, Neuropeptide / physiology
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Urea / analogs & derivatives
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Urea / pharmacology
Substances
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1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
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Benzoxazoles
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Carrier Proteins
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HCRT protein, human
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Intracellular Signaling Peptides and Proteins
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Naphthyridines
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Neuropeptides
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Urea