Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T1R8, Canada; Department of Pharmacology, University of Toronto, Medical Sciences Building RM 4358, 1 King's College Circle, Toronto, Ontario M5S1A8, Canada.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T1R8, Canada.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):906-11. doi: 10.1016/j.bbrc.2014.06.099. Epub 2014 Jun 26.
The μ-δ opioid receptor heteromer activates the pertussis toxin-resistant Gαz GTP-binding protein following stimulation by the δ-agonist deltorphin-II whereas μ- and δ-receptors activate the pertussis toxin-sensitive Gαi3 protein following stimulation by μ- and δ-agonists, respectively. Although the regulation of the μ-δ heteromer is being investigated extensively in vitro, its physiological relevance remains elusive owing to a lack of available molecular tools. We investigated μ-δ heteromer signaling under basal conditions and following prolonged morphine treatment in rodent brain regions highly co-expressing μ- and δ-receptors and Gαz. Deltorphin-II induced Gαz activation in the striatum and hippocampus, demonstrating the presence of μ-δ heteromer signaling in these brain regions. Prolonged morphine treatment, which desensitizes μ- and δ-receptor function, had no effect on μ-δ heteromer signaling in the brain. Our data demonstrate that μ-δ heteromer signaling does not desensitize and is regulated differently from μ- and δ-receptor signaling following prolonged morphine treatment.
μ-δ 阿片受体异源二聚体在 δ-激动剂 δorphin-II 刺激下激活百日咳毒素抗性 Gαz GTP 结合蛋白，而 μ-和 δ-受体在 μ-和 δ-激动剂刺激下分别激活百日咳毒素敏感的 Gαi3 蛋白。尽管 μ-δ 异源二聚体的调节在体外得到了广泛研究，但由于缺乏可用的分子工具，其生理相关性仍然难以捉摸。我们研究了在高表达 μ-和 δ-受体和 Gαz 的啮齿动物脑区中，在基础条件下和在长期吗啡处理后 μ-δ 异源二聚体信号。δorphin-II 在纹状体和海马中诱导 Gαz 激活，证明在这些脑区存在 μ-δ 异源二聚体信号。长期吗啡处理使 μ-和 δ-受体功能脱敏，但对脑内 μ-δ 异源二聚体信号没有影响。我们的数据表明，μ-δ 异源二聚体信号不会脱敏，并且在长期吗啡处理后，其调节方式与 μ-和 δ-受体信号不同。
