PHARMACOLOGICAL CHARACTERISTICS OF POTENTIATION OF 5-HT3 RECEPTORS BYALCOHOLS AND DIETHYL-ETHER IN NCB-20 NEUROBLASTOMA-CELLS

We have examined the actions of alkanols, halogenated ethanol derivati ves and diethyl ether on ion current mediated by 5-HT3 receptors in NC B-20 neuroblastoma cells. The alcohols and diethyl ether potentiated 5 -HT3 receptor-mediated ion current at concentrations that had no effec t on membrane current when applied in the absence of agonist. The pote ncy of alcohols increased with increasing hydrophobicity. However, the maximal efficacy of alcohols was unrelated to hydrophobicity. Interac tions between different drugs applied simultaneously to cells were exa mined to determine whether these compounds compete for a distinct modu latory site associated with the 5-HT3 receptor. Analysis of interactio ns observed at different drug concentrations indicated a variety of in teractions between different compounds, ranging from negative to posit ive allosteric interactions. Interactions between trichloroethanol (TC Et) and isopentanol exhibited characteristics that might indicate comp etition for a single site of action. However, further examination of i nteractions between these two drugs indicated that although isopentano l altered the efficacy of co-applied TCEt, TCR did not have a similar effect with respect to isopentanol. Furthermore, isopentanol did not a lter the potency of TCEt for potentiation of receptor function. The ab sence of competitive interactions among alcohols indicates that a sing le ''alcohol receptor'' cannot be defined using established pharmacolo gic approaches. Our findings are most consistent with the idea that al cohols interact with several hydrophobic sites associated with the 5-H T3 receptor.