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 H(3) receptor ligands in cryostat sections of pig brain. As in other species, binding of the histamine H(3) receptor agonist [(3)H]N(alpha)-methylhistamine was highly heterogeneous in the pig brain, with highest B(max) 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 [(3)H]N(alpha)-methylhistamine was close to 1 nM in all regions of pig brain. Thus, the saturation binding parameters for this H(3) receptor agonist in pig brain were similar to the earlier reports in rat, guinea pig, and human. The distribution of histamine H(3) receptors labeled with the receptor antagonist [(125)I]iodophenpropit in adjacent cryostat sections from the same group of pigs was very similar to that of [(3)H]N(alpha)-methylhistamine. However, the B(max) of the receptor antagonist was 40% higher in the basal ganglia than was the B(max) of the receptor agonist. The K(d) for the receptor antagonist ligand was close to 0.9 nM in all regions. These results suggest that histamine H(3) 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 D(2) receptors.
Mezzomo
Kelin
K
Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Brazil.
Cumming
Paul
P
Minuzzi
Luciano
L
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007550:Isothiuronium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008024:Ligands; D008761:Methylhistamines / Q000008:administration & dosage / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; D008024:Ligands; D008761:Methylhistamines; D018100:Receptors, Histamine H3; D007550:Isothiuronium; C077791:iodophenpropit; D019204:GTP-Binding Proteins; C048140:N-methylhistamine