QUANTITATIVE RECEPTOR AUTORADIOGRAPHY DEMONSTRATES A DIFFERENTIAL DISTRIBUTION OF NEUROPEPTIDE-Y Y-1 AND Y-2 RECEPTOR SUBTYPES IN HUMAN AND RAT-BRAIN

Quantitative receptor autoradiography was performed on sections of rat and human brain using [I-125]peptide YY ([I-125]PYY) to measure the anatomical distribution of neuropeptide Y (NPY) receptors. Masking Y-1- and Y-2-NPY subtypes with the agonists [Leu(31),Pro(34)]NPY and NPY13-35, respectively demonstrated a differential distribution of Y-1 and Y-2 receptors between human and rat brain. In human brain, the highest density of [I-125]PYY binding was found in pyramidal layers (CA4-CA1) of hippocampus, head and tail regions of caudate nucleus, locus coeruleus and substantia nigra. There was moderate [I-125]peptide YY binding to NPY receptors in the molecular layers of the hippocampus, frontal and temporal cerebral cortex, especially in superficial layers, anterior amygdala, central grey and inferior colliculus. Low levels of binding were observed in white matter. The selective Y-1 receptor agonist, [Leu(31),pro(34)]NPY did not effectively reduce [I-125]PYY binding to any human brain region examined except for approximately 20-40% of the binding sites in the molecular layer of the dentate gyrus, layer IV of the frontal cortex and the radiatum and oriens layers of the hippocampal complex. In contrast, the Y-2 agonist, NPY13-36 was effective at reducing [I-125]PYY binding in all human brain regions examined. In rat brain, high densities of [I-125]PYY binding was measured in cerebral cortex, thalamus and inferior colliculus which was sensitive to [Leu(31),pro(34)]NPY. In contrast, high densities of the NPY13-36 sensitive binding was found in the hippocampus, striatum and nucleus accumbens. Medium to low densities of NPY13-36 sensitive binding was found in medulla and pens. This data suggests that human brain contains primarily Y-2-type NPY receptors with only a few regions expressing Y-1-type receptors. No human brain region examined contained solely Y-1-type receptors. In contrast to human brain, rat brain contains regions which express only Y-1 receptors as well as regions containing only Y-2 receptors and regions containing both Y-1 and Y-2 receptors.