IDENTIFICATION OF MULTIPLE NEUROPEPTIDE-Y RECEPTOR SUBTYPES IN THE HUMAN FRONTAL-CORTEX

Recently, we found abundant mRNA and binding sites for neuropeptide Y Y-1-like receptors in the human cerebral cortex. However, an earlier s tudy using indirect labeling methods failed to detect substantial neur opeptide Y-1-like receptor binding in numerous areas of the human brai n, including the cerebral cortex. To resolve the disparity in these fi ndings, we characterized the neuropeptide Y receptor subtypes labeled with [I-125]peptide YY in homogenates of human frontal cortex. Competi tion experiments using 100 pM [I-125]peptide YY binding to human front al cortex homogenates indicated predominantly neuropeptide Y Y-2 recep tors are labeled with this concentration of ligand. However, saturatio n analysis of [I-125]peptide YY binding to frontal cortex membranes re sulted in isotherms best characterized by a two-site fit. Binding of [ I-125]peptide YY to the high affinity (K-d = 40 pM) binding site was p revented using a 100 nM concentration of the neuropeptide Y Y-2 recept or agonist peptide YY-(3-36). By masking the higher affinity site, we found a low affinity [I-125]peptide YY binding site (K-d = 1.4 nM) exh ibiting a pharmacology consistent with a neuropeptide Y Y-1-like recep tor. It appears that neuropeptide Y Y-2 receptors are the predominant subtype labeled with low concentrations of [I-125]peptide YY and that the neuropeptide Y Y-1 receptor is a low affinity [I-125]peptide YY bi nding site in the human frontal cortex. (C) 1997 Elsevier Science B.V.