DIFFERENTIAL BINDING CHARACTERISTICS OF AGONISTS AT 5-HT(3) RECEPTOR RECOGNITION SITES IN NG108-15 NEUROBLASTOMA-GLIOMA CELLS LABELED BY [H-3] (S)-ZACOPRIDE AND [H-3] GRANISETRON

The pharmacological characteristics of 5-HT3 receptor (5-hydroxytrypta mine3 receptor) recognition sites labelled with [H-3]-(S)-zacopride an d [H-3]granisetron in membranes prepared from NG108-15 neuroblastoma-g lioma cells were directly compared to investigate further differences in the binding characteristics of these two radioligands. Competition curves generated with increasing concentrations of 5-HT3 receptor liga nds emphasized the pharmacological similarity of the two recognition s ites labelled by [H-3]-(S)-zacopride and [H-3]granisetron. However, an alysis of the nature of the competition curves indicated that 5-HT3 re ceptor agonists (5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, ph enylbiguanide) and quipazine generated Hill coefficients greater than unity when the 5-HT3 receptor recognition sites were labelled with [H- 3]granisetron whilst these competing compounds displayed Hill coeffici ents of around unity when the sites were labelled with [H-3]-(S)-zacop ride. Competition for either [H-3]-(S)-zacopride or [H-3]granisetron b inding by the 5-HT3 receptor antagonists granisetron and ondansetron g enerated Hill coefficients around unity. Furthermore, addition of unla belled (S)-zacopride (1.0 nM) failed to alter the nature by which quip azine competed for the [H-3]granisetron-labelled 5-HT3 receptor recogn ition site. Consistent with 5-HT3 receptors radiolabelled in rat corti cal membranes, the present studies indicate that [H-3]-(S)-zacopride m ay label a different site on the 5-HT3-receptor complex compared to [H -3]granisetron.