Journal of Neuroscience, Vol 9, 2607-2619, Copyright © 1989 by Society for Neuroscience
Neuropeptide Y receptor binding sites in rat brain: differential autoradiographic localizations with 125I-peptide YY and 125I- neuropeptide Y imply receptor heterogeneity
DR Lynch, MW Walker, RJ Miller and SH Snyder
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Neuropeptide Y (NPY) receptor binding sites have been localized in the rat
brain by in vitro autoradiography using picomolar concentrations of both
125I-NPY and 125I-peptide YY (PYY) and new evidence provided for
differentially localized receptor subtypes. Equilibrium binding studies
using membranes indicate that rat brain contains a small population of
high-affinity binding sites and a large population of moderate-affinity
binding sites. 125I-PYY (10 pM) is selective for high-affinity binding
sites (KD = 23 pM), whereas 10 pM 125I-NPY labels both high- and
moderate-affinity sites (KD = 54 pM and 920 pM). The peptide specificity
and affinity of these ligands in autoradiographic experiments match those
seen in homogenates. Binding sites for 125I-PYY are most concentrated in
the lateral septum, stratum oriens, and radiatum of the hippocampus,
amygdala, piriform cortex, entorhinal cortex, several thalamic nuclei,
including the reuniens and lateral posterior nuclei, and substantia nigra,
pars compacta, and pars lateralis. In the brain stem, 125I-PYY sites are
densest in a variety of nuclei on the floor of the fourth ventricle,
including the pontine central grey, the supragenual nucleus, and the area
postrema. 125I-NPY binding sites are found in similar areas, but relative
levels of NPY binding and PYY binding differ regionally, suggesting
differences in sites labeled by the two ligands. These receptor
localizations resemble the distribution of endogenous NPY in some areas,
but others, such as the hypothalamus, contain NPY immunoreactivity but few
binding sites.
