Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor function

Recent studies suggest that alcohols, volatile anesthetics, and inhaled dru gs of abuse, which enhance gamma -aminobutyric acid, type A, and glycine re ceptor-activated ion channel function, may share common or overlapping mole cular sites of action on these receptors, To investigate this possibility, these compounds were applied singly and in combination to wild-type glycine cu, receptors expressed in Xenopus laevis oocytes, Data obtained from conc entration-response curves of the volatile anesthetic enflurane constructed in the presence and absence of ethanol, chloroform, or toluene were consist ent with competition for a common binding pocket on these receptors, A muta nt glycine receptor, insensitive to the enhancing effects of ethanol but no t anesthetics or inhalants, demonstrated antagonism of anesthetic and inhal ent effects on this receptor. Although ethanol (25-200 mM) had no effect on its own in this receptor, it was able to inhibit reversibly the enhancing effect of enflurane, toluene, and chloroform in a concentration-dependent m anner. These data suggest the existence of overlapping molecular sites of a ction for ethanol, inhalants, and volatile anesthetics on glycine receptors and illustrate the feasibility of pharmacological antagonism of the effect s of volatile anesthetics.