Multiple high-affinity [H]serotonin binding sites in human frontal cortex

High-affinity [³H]serotonin (5-hydroxytryptamine, 5-HT) binding sites from human frontal cortex can be divided into at least 3 pharmacological subtypes (5-HT_1A, 5-HT_1B and 5-HT₃) based on affinity for [³H]serotonin and spiperone. All 3 sites are solubilized by 3% Triton X-100, 1% Tween-80 and can be enriched by serotonin-linked-Sepharose 4B affinity chromatography. However, 5-HT₃ sites are more sensitive to heat inactivation, long-term storage, and sulfhydrylalkylation. The pharmacological profiles are distinct for the spiperone-insensitive 5-HT_1B and 5-HT₃ sites in both human and bovine cortex. In addition, evidence is presented for the existence of a novel, low concentration [³H]serotonin binding site in human cortex.