Characterization and regional distribution of serotonin S2-receptors in human brain

[3H]Ketanserin binding was characterized in vitro in human brain homogenates and the regional distribution of the sites was determined. In human brain, [3H]ketanserin was found to bind on serotonin (5-HT) S2-receptors; only 5-HT antagonists competed with the labelled ligand at nanomolar concentrations; other drugs were much less active or inactive. Special attention was paid to the choice of a displacer, here methysergide, to determine the blank value (non-displaceable binding). [3H]Ketanserin binding in human brain displayed similar binding characteristics to the S2-receptor in the rat frontal cortex, high affinity (Kd 0.69 nM) and relatively slow dissociation rate. The regional distribution of serotonin S2-receptors labelled with [3H]ketanserin was studied in 30 different regions of human brain. The highest number of receptors was measured in the cortex. However, within the cortex the distribution was also inhomogeneous, a much lower number of sites being found in the pre- and post-central gyri. In the dopaminergic areas and the cerebellum the number of sites was quite low, and only few binding sites were detected in the corpus callosum, the medulla and the hypophysis. The large number of serotonin S2-receptors in the human cortex suggests that serotonin has an important role in this brain region.