5-Hydroxytryptamine1 recognition sites in rat brain : heterogeneity of non-5-hydroxytryptamine1A/1C binding sites revealed by quantitative receptor autoradiography

Abstract Quantitative in vitro receptor autoradiography was used to characterize the [ 3 H]5-hydroxytryptamine binding sites which are not sensitive to 8-hydroxy-2-(di- N -propylamino)tetralin, mesulergine and serotonin-5- O -car☐y-methyl-glycyl-tyrosinamide, in a non-5-hydroxytryptamine 1A/1B/1C/1D receptor population, in rat brain. Displacement of [ 3 H]5-hydroxytryptamine [in the presence of 100nM 8-hydroxy-2-(di- N --propyl-amino)tetralinandmesulergine, to block 5-hydroxytryptamine 1A and 5-hydroxytryptamine 1C sites] with (-)pindolol, 5-hydroxy-3(4-1,2,5,6-tetrahydropyridyl)-4-azaindole, sumatriptan and serotonin-5- O -car☐y-methyl-glycyl-tyrosinamide yielded complex competition curves suggesting the presence of 5-hydroxytryptamine 1B and 5-hydroxytryptamine 1D sites and an additional [ 3 H]5-hydroxytryptamine-sensitive component in rat brain. The non-5-hydroxytryptamine 1n1A/1B/1C/1D binding sites were localized in olfactory tubercle, several nuclei of the amygdala, bed nucleus of the stria terminalis, caudate-putamen, CA3 field of the hippocampus, the frontoparietal cortex (motor area) and parts of the striate cortex. All the drugs used had low affinity for the unknown recognition site, which therefore might be comparable to the [ 3 H]5-hydroxytryptamine binding site reported to display low affinity for sumatriptan and 5-car☐amidotryptamine in the brains of various species, the so-called 5-hydroxytryptamine 1E site. A comparison of the density of sites labelled with [ 125 I]serotonin-5- O -car☐y-methyl-glycyl-tyrosinamide (representing 5-hydroxytryptamine 1B and 5-hydroxytryptamine 1D sites) and [ 3 H]5-hydroxytryptamine (under the conditions mentioned above) showed the density of [ 3 H]5-hydroxytryptamine recognition sites to be higher in some structures. It is concluded that in addition to the 5-hydroxytryptamine 1B and 5-hydroxytryptamine 1D , an uniden tified 5-hydroxytryptamine binding site is labelled with [ 3 H]5-hydroxytryptamine, in the presence of 5-hydroxytryptamine 1A and 5-hydroxytryptamine 1C blocking agents, in several structures of the rat brain. Since the compounds tested displayed very low affinity for this site, the availability of high-affinity ligands would certainly facilitate further characterization of this [ 3 H]5-hydroxytryptamine recognition site, which may correspond to the 5-hydroxytryptamine 1E site.