ETHANOL FAILS TO MODIFY (H-3)GR65630 BINDING TO 5-HT3 RECEPTORS IN NCB-20 CELLS AND IN RAT CEREBRAL MEMBRANES

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 membranes from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [H-3]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [H-3]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [H-3]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [H-3]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.