Evidence for in vivo interactions between neuropeptide Y-related peptides and σ receptors in the mouse hippocampal formation

Abstract

Recently, it was proposed that neuropeptide Y (NPY) and peptide YY (PYY) could act as endogenous ligands for σ binding sites, as both NPY and PYY competed with high affinity (nanomolar) for 3H-(+)SKF 10,047 binding sites in rat brain membrane homogenates (Roman et al., 1989). However, various laboratories failed to replicate these in vitro findings. In order to clarify this apparent discrepancy and investigate further possible interactions between NPY and σ related sites, we evaluated the effects of NPY, PYY and homologs, as well as nonrelated peptides, on in vivo 3H-(+)SKF 10,047 binding parameters in the mouse hippocampal formation. As expected, haloperidol (2 mg/kg), a prototypical σ receptor ligand, competed for 90% of in vivo hippocampal labeling observed following a peripheral intravenous injection of 3H-(+)SKF 10,047. Intracerebroventricular injections of 300-3000 pmol of either NPY, PYY, NPY2-36, or the Y1 agonist Leu31,Pro34-NPY inhibited significant proportions (17-35%) of haloperidol-sensitive in vivo 3H-(+)SKF 10,047 hippocampal labeling. However, a Y2 receptor agonist, NPY13-36, and nonrelated peptides such as neurotensin and vasoactive intestinal polypeptide, as well as adrenalin, failed to alter in vivo 3H-(+)SKF 10,047 hippocampal binding. It thus appears that NPY, PYY, and a selective Y1 agonist can interact in a concentration-dependant manner, with in vivo 3H-(+)SKF 10,047 labeling in the mouse hippocampal formation. This effect demonstrates selectivity as a Y2 agonist, unrelated peptides, and adrenalin failed to alter in vivo σ labeling. This in vivo interaction may be relevant to some of the respective biological actions of NPY and σ-related molecules. Copyright © 1993 society for neuroscience.