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

Abstract

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.