阿片受体依赖的信号转导和行为的分子机制。
Molecular mechanisms of opioid receptor-dependent signaling and behavior.
机构信息
Department of Anesthesiology, Washington University School of Medicine, Washington University Pain Center, St. Louis, Missouri 63110, USA.
出版信息
Anesthesiology. 2011 Dec;115(6):1363-81. doi: 10.1097/ALN.0b013e318238bba6.
Abstract
Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibitory G proteins. These receptors form homo- and heterodimeric complexes and signal to kinase cascades and scaffold a variety of proteins.The authors discuss classic mechanisms and developments in understanding opioid tolerance and opioid receptor signaling and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. The authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, the authors conclude there is a continued need for more translational work on opioid receptors in vivo.
摘要
阿片受体作为治疗疼痛及相关疾病的靶点已经有几千年的历史了，而且它们仍然是临床上应用最广泛的镇痛药。μ、κ 和 δ 阿片受体是最初分类的受体亚型，而阿片受体样-1（ORL1）是特征最少的受体。这四种受体都是 G 蛋白偶联的，并激活抑制性 G 蛋白。这些受体形成同型和异型二聚体复合物，并信号转导至激酶级联反应和支架各种蛋白质。作者讨论了理解阿片类药物耐受和阿片受体信号转导的经典机制和进展，并强调了阿片类药物分子药理学、行为药理学和人类遗传学的进展。作者将阿片受体信号转导如何导致行为调节的潜在治疗干预置于上下文中。最后，作者得出结论，需要在体内对阿片受体进行更多的转化研究。
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