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.
Wong
E H
EH
Department of Neurosciences, Syntex Discovery Research, Palo Alto, CA 94304.
Bonhaus
D W
DW
Lee
J A
JA
Wu
I
I
Loury
D N
DN
Eglen
R M
RM
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D017829:Granisetron / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D011814:Quipazine / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017829:Granisetron; D007093:Imidazoles; D007211:Indoles; D011814:Quipazine; D012702:Serotonin Antagonists; C059068:GR 65630