Analysis of the effects of anesthetics and ethanol on μ-Opioid receptor

G protein-coupled receptors,in particular,ca2+-mobilizing gq-coupled receptors have been reported to be targets for anesthetics. opioids are commonly used analgesics in clinical practice,but the effects of anesthetics on the opioid μ-receptors (μor) have not been systematically examined. we report here an electrophysiological assay to analyze the effects of anesthetics and ethanol on the functions of μor in xenopus oocytes expressing a μor fused to chimeric gα protein gqi5 (μor-gqi5). using this system,the effects of halothane,ketamine,propofol,and ethanol on the μor functions were analyzed. in oocytes expressing μor-gqi5,the μor agonist damgo ([d-ala2,n-mephe4,gly-ol]-enkephalin) elicited ca2+-activated cl- currents in a concentration-de-pendent manner (ec50 = 0.24 μm). ketamine,propofol,halothane,and ethanol themselves did not elicit any currents in oocytes expressing μor-gqi5,whereas ketamine and ethanol inhibited the damgo-induced cl- currents at clinically equivalent concentrations. propofol and halothane in-hibited the damgo-induced currents only at higher concentrations. these findings suggest that ketamine and ethanol may inhibit μor functions in clinical practice. we propose that the electro-physiological assay in xenopus oocytes expressing μor-gqi5 would be useful for analyzing the effects of anesthetics and analgesics on opioid receptor function. ©2010 the japanese pharmacological society.