DIFFERENT DENSITIES OF 5-HT(3) RECEPTORS ARE LABELED BY [H-3] QUIPAZINE, [H-3] GR-65630 AND [H-3] GRANISETRON

The binding of three, structurally distinct 5-hydroxytryptamine3 (5-HT 3) receptor radioligands was characterized in rat cerebral cortex, rab bit ileum myenteric plexus and NG- 108- 1 5 neuroblastoma cells. The d ensity of sites labeled by the three ligands in rat cortex or in rabbi t ileum was markedly different. [H-3]Quipazine labeled more sites than [H-3]GR 65630 in rat cortex (4.0-fold) and rabbit ileum (1.9-fold), b ut not in NG-108-15 cells. [H-3]Quipazine also labeled a greater densi ty of sites than [H-3]granisetron in rat cortex (7-fold) but not in NG -108 cells. [H-3]Quipazine binding in rat cortex and rabbit ileum, but not in NG-108-15 cells, was displaced by non-radiolabeled GR 65630 in a consistent with an interaction with more than one site. These data indicate that not all 5-HT3 receptor radioligands recognize the same p opulation of 5-HT3 binding sites with equivalent density and further s uggest the existence of subtypes of 5-HT3 receptor binding sites in mt cortical and rabbit myenteric plexus preparations.