Different densities of 5-HT3 receptors are labeled by [3H]quipazine, [3H]GR 65630 and [3H]granisetron.

The binding of three, structurally distinct, 5-hydroxytryptamine3 (5-HT3) receptor radioligands was characterized in rat cerebral cortex, rabbit ileum myenteric plexus and NG-108-15 neuroblastoma cells. The density of sites labeled by the three ligands in rat cortex or in rabbit ileum was markedly different. [3H]Quipazine labeled more sites than [3H]GR 65630 in rat cortex (4.0-fold) and rabbit ileum (1.8-fold), but not in NG-108-15 cells. [3H]Quipazine also labeled a greater density of sites than [3H]granisetron in rat cortex (7-fold) but not in NG-108 cells. [3H]Quipazine binding in rat cortex and rabbit ileum, but not in NG-108-15 cells, was displaced by non-radiolabeled GR 65630 in a manner consistent with an interaction with more than one site. These data indicate that not all 5-HT3 receptor radioligands recognize the same population of 5-HT3 binding sites with equivalent density and further suggest the existence of subtypes of 5-HT3 receptor binding sites in rat cortical and rabbit myenteric plexus preparations.