Cox Brian M, Christie Macdonald J, Devi Lakshmi, Toll Lawrence, Traynor John R
Department of Pharmacology, Uniformed Services University, Bethesda, MD, USA.
Br J Pharmacol. 2015 Jan;172(2):317-23. doi: 10.1111/bph.12612. Epub 2014 Jul 1.
Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms.
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
阿片受体结构与功能研究的最新进展,给个体受体类型的定义以及精确描述可能在体内发挥不同功能的亚型的命名法的制定带来了重大挑战。在澳大利亚凯恩斯举行的2013年国际麻醉品研究会议上的报告,探讨了一些正在揭示阿片受体信号传导复杂性的新发现。阿片受体信使核糖核酸的可变加工可能导致μ受体存在多种亚型。每种阿片受体类型既可以作为单体发挥作用,也可以作为同二聚体、异二聚体或更高聚体的一部分发挥作用。此外,最近的证据表明,通过μ受体激活的信号转导途径中存在激动剂偏向性,并且受体上存在调节性变构位点。本简要综述总结了近期的发现,这些发现对受体定义以及特定受体形式激活的信号转导途径的表征提出了挑战。
本文是关于阿片类药物:功能选择性新途径的主题部分的一部分。要查看本部分的其他文章,请访问http://dx.doi.org/10.1111/bph.2015.172.issue-2。