Direct autoradiographic determination of M1 and M2 muscarinic acetylcholine receptor distribution in the rat brain: relation to cholinergic nuclei and projections

Abstract

The autoradiographic distributions of receptors with high affinity for [3H]oxotremorine-M (the M2 receptor) and [3H]pirenzepine (the M1 receptor) were studied in the rat brain. M1 receptors were seen in highest density only in telencephalic structures: cerebral cortex (layers I-II), hippocampus, dentate gyrus, medial and basolateral amygdala, nucleus accumbens and caudate/putamen. M2 receptors were detected throughout the brain, with highest levels observed in cerebral cortical layers III and V, forebrain cholinergic nuclei, caudate/putamen, various thalamic areas, inferior and superior colliculus, interpeduncular and pontine nuclei, brainstem cholinergic nuclei and cervical spinal cord regions. M2 receptors were found to be good markers for cholinergic cell groups and the majority of cholinergic projection areas, whereas M1 receptors were only found in a large sub-group of telencephalic cholinergic projection areas, and the pattern of distribution of receptors in these areas differed from that of M2 receptors. Scatchard analysis of [3H]oxotremorine-M binding to inferior collicular slices revealed one site with a dissociation constant (Kd) of 1.9 nM and a receptor density (Bmax) of 1.4 pmol/mg protein. Our data support the hypothesis that M1 and M2 receptors are physically distinct sub-types of the muscarinic acetylcholine receptor.