title: Chlorpromazine and QX222 block 5-HT3 receptors in N1E-115 neuroblastoma cells.
abstract: The effects of chlorpromazine and the lidocaine derivative QX222, which block nicotinic acetylcholine receptors, were examined on 5-HT3 receptors in N1E-115 mouse neuroblastoma cells, using whole cell voltage-clamp and radioligand binding. Electrophysiological studies examining the effects of chlorpromazine and QX222 on 5-HT3 agonist-induced responses revealed IC50s of 0.2 and 8.5 microM respectively. The action was not voltage- or use-dependent and there was no blocking action when chlorpromazine was applied from inside the cell. Chlorpromazine and QX222 inhibited the binding of a radiolabelled 5-HT3 receptor antagonist, [3H]GR65630, with IC50s of 0.9 and 29 microM respectively. Scatchard plots revealed a decrease in affinity (Kd) in the presence of chlorpromazine, but no change in the maximum number of binding sites (Bmax). The results suggest differential actions of the compounds at 5-HT3 and acetylcholine receptors.
authors.affiliation: Division of Neurobiology, Laboratory of Molecular Biology, MRC Centre, Cambridge, U.K.
authors.forename: M I
authors.initials: MI
authors.lastname: Sepúlveda
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: S C
authors.initials: SC
authors.lastname: Lummis
mesh_terms: D000345:Affinity Labels; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology*; D004594:Electrophysiology; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010777:Photochemistry; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000345:Affinity Labels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C006072:QX-222; D012701:Serotonin; D008012:Lidocaine; D002746:Chlorpromazine