title: High specificity of human orexin receptors for orexins over neuropeptide Y and other neuropeptides.
abstract: Orexin- and neuropeptide Y-ergic systems show physiological interaction in the regulation of appetite. In this study we investigate the postulated effect of neuropeptide Y (NPY) and other peptides directly on orexin OX1 and OX2 receptors. None of the tested peptides (NPY-variants, secretin, alpha-melanocortin, pancreatic polypeptide or pituitary adenylyl cyclase-activating peptide-38) induced any Ca2+ elevation at the concentrations up to 300 nM (human NPY, secretin and alpha-melanocortin up to 1 microM). Orexin-A- and -B-mediated Ca2+ elevations were completely unaffected by the peptides. In binding assays, human NPY, secretin and alpha-melanocortin at 1 microM did not induce any displacement of 0.1 nM [125I]orexin-A. Thus, in contrast to the previously reported result on orexin-A binding, our results demonstrate that NPY does not directly interact with orexin receptor in intact cellular settings.
authors.affiliation: Department of Physiology, Division of Cell Physiology, Uppsala University, BMC, P.O. Box 572, S-75123, Uppsala, Sweden. tomas.holmqvist@fysiologi.uu.se
authors.forename: T
authors.initials: T
authors.lastname: Holmqvist
authors.forename: K E
authors.initials: KE
authors.lastname: Akerman
authors.forename: J P
authors.initials: JP
authors.lastname: Kukkonen
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide