IDENTIFICATION OF A RECEPTOR PROTEIN FOR NEUROPEPTIDE-Y IN RABBIT KIDNEY - G-PROTEIN ASSOCIATION AND INHIBITION OF ADENYLATE-CYCLASE

We previously identified the receptor for neuropeptide Y (NPY) on rabbit kidney membranes as a 100 kDa protein [(1990) J. Biol. Chem. 265, 18142-18143]. It is demonstrated in this study that the stable guanine nucleotide analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), is capable of decreasing the labeling of the 100 kDa protein in a concentration-dependent manner, with an IC50 value of 50-mu-M. This suggests that the 100 kDa protein represents a G-protein coupled receptor type. In isolated proximal tubules from rabbit kidney NPY decreases the parathyroid hormone stimulated cAMP production in a dose-dependent fashion. This indicates that the NPY receptor in rabbit kidney is negatively coupled to adenylate cyclase by a G1-like protein.