Analysis of the Effects of Anesthetics and Ethanol on mu-Opioid Receptor

作者：Minami Kouichiro; Sudo Yuka; Shiraishi Seiji; Seo Masanori; Uezono Yasuhito

来源：Journal of Pharmacological Sciences, 2010, 112(4): 424-431.

DOI：10.1254/jphs.10003FP

• mu-opioid receptor
• G(i/o)-coupled receptor
• ketamine
• ethanol
• Xenopus oocyte

G protein coupled receptors, in particular, Ca(2+)-mobilizing G(q)-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 mu-receptors (mu OR) have not been systematically examined. We report here an electrophysiological assay to analyze the effects of anesthetics and ethanol on the functions of mu OR in Xenopus oocytes expressing a mu OR fused to chimeric G alpha protein G(qi5) (mu OR-G(qi5)). Using this system, the effects of halothane, ketamine, propofol, and ethanol on the mu OR functions were analyzed. In oocytes expressing mu OR-G(qi5). the mu OR agonist DAMGO ([D-Ala(2),N-MePhe(4),Gly-ol]-enkephalin) elicited Ca(2+)-activated Cl(-) currents in a concentration-dependent manner (EC(50) = 0.24 mu M). Ketamine, propofol, halothane, and ethanol themselves did not elicit any currents in oocytes expressing mu OR-G(qi5), whereas ketamine and ethanol inhibited the DAMGO-induced Cl(-) currents at clinically equivalent concentrations. Propofol and halothane inhibited the DAMGO-induced currents only at higher concentrations. These findings suggest that ketamine and ethanol may inhibit mu OR functions in clinical practice. We propose that the electro-physiological assay in Xenopus oocytes expressing mu OR-G(qi5) would be useful for analyzing the effects of anesthetics and analgesics on opioid receptor function.

• 出版日期2010-4