Cortical and striatal variations in drug competition studies with putative 5-hydroxytryptamine1D binding sites

The ability of 5-hydroxytryptamine (5-HT), 5-carboxytryptamine (5-CT) and sumatriptan to compete for [3H]5-HT binding sites in various brain tissues was analyzed in bovine, guinea pig, pig and human cortex and caudate. Radioligand binding conditions were designed to allow for the selective labeling of putative 5-HT1D binding sites. 5-HT competed monophasically with putative 5-HT1D binding sites in each of the 8 tissues studied. By contrast, both 5-CT and sumatriptan competed with markedly shallow displacement curves in each of the 8 tissues. In the case of sumatriptan, complete displacement of [3H]5-HT could not be achieved even at concentrations as high as 2000 times its IC50 value. These data indicate that 10(-5) M 5-HT should not be used to define specific binding to 5-HT1D receptors in radioligand binding assays. Instead, 5-HT1D receptor binding sites should be redefined as [3H]5-HT-labeled binding sites displaced by 10(-5) M sumatriptan.