Effects of interferon-alpha on cloned opioid receptors expressed in Xenopus oocytes.

Interferon-alpha (IFNalpha) affects the opioid system. However, the direct action of IFNalpha on cloned opioid receptors remains unknown. Taking advantage of the functional coupling of cloned opioid receptors to G protein-activated inwardly rectifying K+ (GIRK) channels in a Xenopus oocyte expression system, we investigated the effects of recombinant IFNalpha on cloned mu-, delta- and kappa-opioid receptors. In oocytes co-injected with mRNAs for either the delta- or kappa-opioid receptor and for GIRK channel subunits, IFNalpha at high concentrations induced small GIRK currents that were abolished by naloxone, an opioid-receptor antagonist, compared with the control responses to each selective opioid agonist. Additionally, IFNalpha induced no significant current response in oocytes injected with mRNA(s) for either opioid receptor alone or GIRK channels. In oocytes expressing the mu-opioid receptor and GIRK channels, IFNalpha had little or no effect. Moreover, in oocytes expressing each opioid receptor and GIRK channels, GIRK current responses to each selective opioid agonist were not affected by the presence of IFNalpha, indicating no significant antagonism of IFNalpha toward the opioid receptors. Furthermore, IFNalpha had little or no effect on the mu/delta-, delta/kappa- or mu/kappa-opioid receptors expressed together with GIRK channels in oocytes. Our results suggest that IFNalpha weakly activates the delta and kappa-opioid receptors. The direct activation of the delta- and kappa-opioid receptors by IFNalpha may partly contribute to some of the IFNalpha effects under its high-dose medication.