Heterogeneity of muscarinic cholinergic receptors in the developing human fetal brain: regional distribution and characterization

The ontogeny of muscarinic cholinergic receptors has been studied in different regions of the human fetal brain. For a comparison, the same study has been carried out on newborn and premature brain. Regarding on the areas examined (frontal cortex, cerebellum, hippocampus, thalamus and basal ganglia) either an increase or a decrease of receptor density during gestation was observed. Thus, the ontogeny of the receptors follows a different pattern in areas which differ in function, cholinergic innervation and embryological origin. However, in all the regions the affinity of the binding site for the ligand [ 3h]quinuclidinyl benzilate [ 3h]QNB was very similar to that reported for muscarinic receptors from adult mammalian brain. Data obtained from agonist binding (acetylcholine and carbachol) revealed the presence of a high (H)- and a low-affinity binding site (L) from 10 weeks of gestation. The selective antagonist pirenzepine (PZ) also distinguished two different muscarinic receptor subtypes, which however had higher affinity than that seen in adult brain. In conclusion, during ontogeny, the muscarinic acetylcholine receptor shares some but not all of the pharmacological properties shown in the adult brain.