One subunit of the 5-hydroxytryptamine3 (5-HT3) receptor has been cloned, and expression of cDNA coding for this protein in Xenopus oocytes results in the formation of homomeric ion channels. In the present study, this system was used to define the sensitivity of the 5-HT3 receptor to alcohols and anesthetics. Ethanol, in pharmacologically relevant concentrations, potentiated 5-HT-mediated currents, with the greatest potentiation observed at lower concentrations of 5-HT. Likewise, butanol stimulated the receptor but with greater efficacy and potency than ethanol. The volatile anesthetics isoflurane, halothane and 1,2,2- trifluorocyclobutane (F3) all enhanced 5-HT3 receptor function. Concentrations 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 ethanol in enhancing 5-HT3 receptor function. In the presence of 0.5 μM 5-HT, maximal stimulation by ethanol was ~50%, but anesthetic enhancement of 5-HT3 receptor-mediated currents did not reach a maximum. Over the concentrations tested, anesthetics potentiated 0.5 μM 5-HT-mediated currents by ~25% to 400%. The intravenous anesthetic propofol did not enhance 5-HT3 receptor function or change the potentiation of this receptor by halothane. These results suggest that alcohols and volatile anesthetics have similar actions on 5-HT3 receptor function, which is in agreement with results of studies with other members of the superfamily of ligand-gated ion channels. We suggest that these actions may cause the nausea and emesis produced by volatile anesthetics.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1994|