title: Ethanol fails to modify [3H]GR65630 binding to 5-HT3 receptors in NCB-20 cells and in rat cerebral membranes.
abstract: Low concentrations of ethanol have been found to enhance the electrophysiologic effect of serotonin (5-HT) acting at 5-HT3 receptors on NCB-20 cells. To determine whether this action of ethanol reflects a change in the agonist-receptor interaction, the effect of ethanol (100 mM) on agonist and antagonist binding to 5-HT3 receptor was studied in vitro in membrane from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [3H]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [3H]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [3H]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [3H]GR65630 binding by 5-HT was approximately 30%. Ethanol decreased the affinity of the receptor for 2-methyl-5-HT, but not to 5-HT in NCB-20 cells, and had no effect on agonist binding in brain membranes. The results indicate that enhancement of 5-HT responses at 5-HT3 receptors by ethanol is not a result of changes in the equilibrium binding characteristics of the agonist.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, Rockville, Maryland.
authors.forename: K
authors.initials: K
authors.lastname: Hellevuo
authors.forename: P L
authors.initials: PL
authors.lastname: Hoffman
authors.forename: B
authors.initials: B
authors.lastname: Tabakoff
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002461:Cell Line, Transformed; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007093:Imidazoles; D007211:Indoles; D011985:Receptors, Serotonin; C059068:GR 65630; D000431:Ethanol