Muscarinic cholinergic receptors: Autoradiographic localization of high and low affinity agonist binding sites

Abstract

Previous studies have shown that muscarinic cholinergic agonists bind to 3 distinct receptor sites in brain, each being distinguished by their affinity for the agonists. Antagonists, on the other hand, bind to these sites with the same high affinity. The relative concentrations of the two high and the low affinity agonist sites are known to vary in different brain regions. The goal of this study was to localize separate populations of high and low affinity receptor sites in brain at the light microscopic level. All muscarinic receptors in slide-mounted intact tissue sections were labeled with [ 3H]N-methyl scopolamine ([ 3H]NMS), but in some experiments carbachol was added to selectively inhibit the binding of [ 3H]NMS to the high affinity sites. Autoradiograms of these tissue sections were generated by the apposition of emulsion-coated coverslips. Certain brain areas showed a relatively large displacement of [ 3H]NMS by carbachol indicating high concentrations of high affinity agonist binding sites. These areas included lamina IV of the cerebral cortex, nucleus tractus diagonalis, some thalamic nuclei, the zona incerta and the dorsal lateral geniculate body.