Ontogeny of muscarinic receptors in the rat brain with emphasis on the differentiation of M1- and M2-subtypes--semi-quantitative in vitro autoradiography.

The ontogeny of muscarinic acetylcholine receptors (mAChR) in the rat brain was studied with emphasis on the differentiation of M1- and M2-receptor subtypes through semi-quantitative in vitro autoradiography. [3H]Quinuclidinyl benzilate (QNB) and [3H]pirenzepine (PZ) were used for labeling total mAChR and M1-receptors, respectively. In the cerebral cortex of adult rats, [3H]QNB binding sites were more richly present in the superficial and deeper layers than in the middle layer, while M1-receptors were diffusely observed in all the layers. This means that M2-receptors are highly concentrated in the superficial and deeper layers. The ontogenetical differentiation of the laminar distribution between M1- and M2-receptors first appeared at 14 days of postnatal age. In the hippocampus and striatum whose mAChR were predominantly of the M1-type in the adult rat brain, ontogenic patterns of M1-receptors were almost identical to those of total mAChR. On the other hand, mAChR in the cerebellar cortex and lower brainstem of the adult rat were mainly of the M2-subtype. In these areas, the ontogeny of total mAChR was apparently observed. However, M1-receptors were not observed at any stage of the ontogeny. The above-mentioned results indicate that M1- and M2-receptors show distinct developmental behaviors in the rat brain.