[3H] Ketanserin binds to non-5-HT2 sites in rabbit cerebral cortex and neostriatum

A characterization of ³H]ketanserin (³H]KTS) binding in the frontal cortex (fCTX) and neostriatum (caudate-putamen, CPU) of rabbit was carried out to determine whether this ligand labels a non-serotoninergic receptor. The association and dissociation kinetics in fCTX were rapid, and could be fitted to two-site models, suggesting ³H]KTS is labeling two cortical sites. Using the serotonin-2 (5-HT₂) antagonist mianserin to determine nonspecific binding, the saturation curves revealed a single high-affinity binding site. In contrast, when unlabeled ketanserin was used for nonspecific counts, the Scatchard plots were best fitted to a two-site model but the binding parameters of the high-affinity site were similar to that obtained in the presence of mianserin. The 5-HT₂ antagonists mianserin, methysergide and ritanserin inhibited ³H]KTS binding in fCTX at nanomolar concentrations, however, the curves were best fitted to two-site models. In contrast, ³H]KTS binding to membrane preparations from the CPU could only be inhibited by high (micromolar) concentrations of these antagonists. Low micromolar concentrations of the monoamine uptake blockers GBR12909, desipramine, nomifensine, cocaine and fluoxetine competed with ³H]KTS in both fCTX and CPU. This study demonstrates that ³H]KTS labels a non-serotoninergic recognition site in the rabbit fCTX and CPU similar to that found in the rat neostriatum, i.e.: probably a monoamine transport site.