Identification of 5‐hydroxytryptamine_1D binding sites in human brain membranes

High‐affinity, specific ³H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT_1A and 5‐HT_1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT₁ sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP > GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5‐HT_1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5‐HT_1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by ³H‐5‐HT in the presence of 100 nM 8‐OH‐DPAT + 100 nM mesulergine. We conclude that the majority of ³H‐5‐HT‐labeled recognition sites in human cortex, caudate, and globus pallidus represent 5‐HT_1D binding sites.