Autoradiographic characterisation of [35S]GTPγS binding stimulation mediated by 5-HT1B receptor in postmortem human brain

G-protein activation mediated by 5-HT1B receptors was studied in human brain by [35S]GTPγS autoradiographic methods. 5-HT (10 μM) increased [35S]GTPγS binding in caudate-putamen nucleus, globus pallidus, dentate gyrus, CA1, entorhinal cortex and substantia nigra. In basal ganglia and midbrain, this effect was blocked by GR 127935 (5-HT1B/1D antagonist). In contrast, WAY 100635 (selective 5-HT1A antagonist) reversed the effect of 5-HT in hippocampus and entorhinal cortex. Therefore, a detailed pharmacological study was carried out in basal ganglia and substantia nigra using 5-HT and the 5-HT1B/1D agonists GTI and CP 93129. In these areas, these agonists stimulated [35S]GTPγS binding in a concentration-dependent manner, with no significant differences in the potency for a given structure. Furthermore, GTI was more potent in the putamen than in globus pallidus. In caudate-putamen, the three agonists showed the same efficacy, while in globus pallidus and substantia nigra the efficacy of 5-HT was higher than GTI and CP 93129. The selective 5-HT1B antagonist SB-224289 inhibited GTI- and CP 93129-stimulated [35S]GTPγS binding in basal ganglia and substantia nigra, while coincubation with BRL 15572 (selective 5-HT1D antagonist) did not result in any significant change. Here we report the anatomical pattern of distribution of 5-HT1B-dependent functionality by using specific pharmacological tools in human brain sections.