Comparison of the binding distribution of agonist and antagonist ligands for histamine H3 receptors in pig brain by quantitative autoradiography

The relationship between the abundances of agonist and antagonist-binding sites for monoamine receptors is poorly established. Therefore, we used quantitative autoradiography to investigate the distribution and concentration of binding sites for histamine H3 receptor ligands in cryostat sections of pig brain. As in other species, binding of the histamine H3 receptor agonist [3H]Nα-methylhistamine was highly heterogeneous in the pig brain, with highest Bmax in the substantia nigra, followed by the nucleus accumbens and caudate, intermediate binding in frontal cortex, diencephalon, and mesencephalon, and absent specific binding in cerebellum: the affinity of [3H]Nα-methylhistamine was close to 1 nM in all regions of pig brain. Thus, the saturation binding parameters for this H3 receptor agonist in pig brain were similar to the earlier reports in rat, guinea pig, and human. The distribution of histamine H3 receptors labeled with the receptor antagonist [125I]iodophenpropit in adjacent cryostat sections from the same group of pigs was very similar to that of [3H]Nα-methylhistamine. However, the Bmax of the receptor antagonist was 40% higher in the basal ganglia than was the Bmax of the receptor agonist. The Kd for the receptor antagonist ligand was close to 0.9 nM in all regions. These results suggest that histamine H3 receptor agonist-binding sites, i.e. those linked to intracellular G-protein, comprise a subset of the total receptor antagonist-binding sites in the basal ganglia, as has been reported for dopamine D2 receptors.