Kobayashi Toru, Washiyama Kazuo, Ikeda Kazutaka
Department of Molecular Neuropathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata, Niigata 951-8585, Japan.
Life Sci. 2004 Dec 10;76(4):407-15. doi: 10.1016/j.lfs.2004.09.007.
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.
α干扰素（IFNα）会影响阿片系统。然而，IFNα对克隆的阿片受体的直接作用尚不清楚。利用爪蟾卵母细胞表达系统中克隆的阿片受体与G蛋白激活的内向整流钾离子（GIRK）通道的功能偶联，我们研究了重组IFNα对克隆的μ、δ和κ阿片受体的影响。在共注射δ或κ阿片受体以及GIRK通道亚基mRNA的卵母细胞中，与每种选择性阿片激动剂的对照反应相比，高浓度的IFNα诱导出小的GIRK电流，该电流可被阿片受体拮抗剂纳洛酮消除。此外，单独注射阿片受体或GIRK通道mRNA的卵母细胞中，IFNα未诱导出明显的电流反应。在表达μ阿片受体和GIRK通道的卵母细胞中，IFNα几乎没有影响。而且，在表达每种阿片受体和GIRK通道的卵母细胞中，IFNα的存在不影响GIRK对每种选择性阿片激动剂的电流反应，表明IFNα对阿片受体无明显拮抗作用。此外，IFNα对与GIRK通道一起在卵母细胞中共同表达的μ/δ、δ/κ或μ/κ阿片受体几乎没有影响。我们的结果表明，IFNα可微弱激活δ和κ阿片受体。IFNα对δ和κ阿片受体的直接激活可能部分促成了其高剂量用药时的某些效应。
