Muscarinic cholinergic receptors in human infant forebrain: [ 3H]Quinuclidinyl benzilate binding in homogenates and quantitative autoradiography in sections

Abstract

The ontogeny of muscarinic receptors in human brain was studied by comparing [ 3H]quinuclidinyl benzilate ([ 3H]QNB) binding in postmortem tissue from infants 1 week to 3 months of age with binding in adult specimens. Saturation analysis with [ 3H]QNB and displacement studies with muscarinic antagonists and agonists in tissue homogenates demonstrated that binding sites in the infants' forebrain regions were present in adult or higher than adult concentrations (B max). Binding affinity ( K d ) and pharmacological characteristics were nearly identical at the two ages. Quantitative receptor autoradiography demonstrated more [ 3H]QNB binding in the gray matter of infants than adults and revealed a marked difference between the two ages in the laminar distribution of binding sites in neocortex. In contrast to the adult pattern with higher binding in superficial layers 1–3 than in layers 4–6, the distribution in the immature cortex was inverted. These results suggest that muscarinic receptors in infants resemble closely those in mature brain. However, the topography of receptors in the immature neocortex is distinct and they are redistributed in a gradient from inside outward during postnatal development.