Differential binding characteristics of agonists at 5-HT3 receptor recognition sites in NG108-15 neuroblastoma-glioma cells labelled by [3H]-(S)-zacopride and [3H]granisetron.
The pharmacological characteristics of 5-HT3 receptor (5-hydroxytryptamine3 receptor) recognition sites labelled with [3H]-(S)-zacopride and [3H]granisetron in membranes prepared from NG108-15 neuroblastoma-glioma 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 ligands emphasized the pharmacological similarity of the two recognition sites labelled by [3H]-(S)-zacopride and [3H]granisetron. However, analysis of the nature of the competition curves indicated that 5-HT3 receptor agonists (5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, phenylbiguanide) and quipazine generated Hill coefficients greater than unity when the 5-HT3 receptor recognition sites were labelled with [3H]granisetron whilst these competing compounds displayed Hill coefficients of around unity when the sites were labelled with [3H]-(S)-zacopride. Competition for either [3H]-(S)-zacopride or [3H]granisetron binding by the 5-HT3 receptor antagonists granisetron and ondansetron generated Hill coefficients around unity. Furthermore, addition of unlabelled (S)-zacopride (1.0 nM) failed to alter the nature by which quipazine competed for the [3H]granisetron-labelled 5-HT3 receptor recognition site. Consistent with 5-HT3 receptors radiolabelled in rat cortical membranes, the present studies indicate that [3H]-(S)-zacopride may label a different site on the 5-HT3-receptor complex compared to [3H]granisetron.
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, U.K.
J M
JM
Barnes
N M
NM
Barnes
D000818:Animals; D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology*; D001645:Biguanides / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds / Q000378:metabolism / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D005910:Glioma / Q000378:metabolism* / Q000648:ultrastructure; D017829:Granisetron; D007191:Indazoles / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure; D017294:Ondansetron / Q000378:metabolism; D011814:Quipazine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D001549:Benzamides; D001645:Biguanides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017829:Granisetron; D007191:Indazoles; D017294:Ondansetron; D011814:Quipazine; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; C055971:zacopride; C008846:phenyl biguanide