ALCOHOLS AND ANESTHETICS ENHANCE THE FUNCTION OF 5-HYDROXYTRYPTAMINE(3) RECEPTORS EXPRESSED IN XENOPUS-LAEVIS OOCYTES

One subunit of the 5-hydroxytryptamine(3) (5-HT3) receptor has been cl oned, and expression of cDNA coding for this protein in Xenopus oocyte s results in the formation of homomeric ion channels. In the present s tudy, this system was used to define the sensitivity of the 5-HT3 rece ptor to alcohols and anesthetics. Ethanol, in pharmacologically releva nt concentrations, potentiated 5-HT-mediated currents, with the greate st potentiation observed at lower concentrations of 5-HT. Likewise, bu tanol stimulated the receptor but with greater efficacy and potency th an ethanol. The volatile anesthetics isoflurane, halothane and 1,2,2-t rifluorocyclobutane (F3) all enhanced 5-HT3 receptor function. Concent rations of these anesthetics below the minimal alveolar concentration for anesthesia (MAC) produced significant stimulation of 5-HT-mediated currents. Similar to the alcohols, the greatest enhancement of 5-HT3 receptor function by anesthetics was seen at lower concentrations of 5 -HT. However, anesthetics were substantially more efficacious than eth anol in enhancing 5-HT3 receptor function. In the presence of 0.5 mu M 5-HT, maximal stimulation by ethanol was similar to 50%, but anesthet ic enhancement of 5-HT3 receptor-mediated currents did not reach a max imum. Over the concentrations tested, anesthetics potentiated 0.5 mu M 5-HT-mediated currents by similar to 25% to 400%. The intravenous ane sthetic propofol did not enhance 5-HT3 receptor function or change the potentiation of this receptor by halothane. These results suggest tha t alcohols and volatile anesthetics have similar actions on 5-HT3 rece ptor function, which is in agreement with results of studies with othe r members of the superfamily of ligand-gated ion channels. We suggest that these actions may cause the nausea and emesis produced by volatil e anesthetics.