High specificity of human orexin receptors for orexins over neuropeptide Yand other neuropeptides

Orexin- and neuropeptide Y-ergic systems show physiological interaction in the regulation of appetite. In this study we investigate the postulated eff ect of neuropeptide Y (NPY) and other peptides directly on orexin OX1 and O X2 receptors. None of the tested peptides (NPY-variants, secretin, alpha -m elanocortin, pancreatic polypeptide or pituitary adenylyl cyclase-activatin g peptide-38) induced any Ca2+ elevation at the concentrations up to 300 nM (human NPY, secretin and a-melanocortin up to 1 muM). Orexin-A- and -B-med iated Ca2+ elevations were completely unaffected by the peptides. In bindin g assays, human NPY, secretin and alpha -melanocortin at 1 muM did not indu ce any displacement of 0.1 nM [I-125]orexin-A. Thus, in contrast to the pre viously reported result on orexin-A binding, our results demonstrate that N PY does not directly interact with orexin receptor in intact cellular setti ngs. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.