High specificity of human orexin receptors for orexins over neuropeptide Y and other neuropeptides.

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.