Opioid Receptors and Signaling on Cells from the Immune System
Opioid Receptors and Signaling on Cells from the Immune System
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DOI：
10.1007/s11481-006-9026-2
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发表时间：
2006-09-01
影响因子：
6.2
通讯作者：
Tipton, Christopher M.
中科院分区：
文献类型：
--
作者：
Bidlack, Jean M.;Khimich, Maxim;Tipton, Christopher M.
这篇综述讨论了确定结合位点或功能反应是否直接由μ，δ或κ阿片受体介导的标准。1988年，Sibinga和Goldstein发表了第一篇关于免疫系统细胞是否表达阿片受体的综述。他们使用的标准，即结构-活性关系、立体选择性、剂量和浓度依赖性以及饱和度，今天仍然是确定免疫应答是否由μ、δ或κ阿片受体介导的相关标准。放射性配体受体结合研究和功能研究，清楚地表明免疫细胞上的阿片受体的存在。选择性激动剂和拮抗剂的μ，δ和κ阿片受体进行了讨论，并强调其在实验中使用的需要。功能测定中使用的条件非常重要。受体脱敏和下调发生在应用激动剂后几分钟内。然而，许多免疫学测定在测量免疫学效应之前应用激动剂数天。获得的结果可能反映了受体脱敏和/或下调的结果，而不是在受体急性激活时观察到的变化。受体药理学的未来在于G蛋白偶联受体的串扰和二聚化。在转染系统中，阿片受体已被证明与趋化因子和大麻素受体二聚化，导致不同类型的受体之间的串扰。
This review discusses the criteria for determining whether a binding site or functional response is directly mediated by either the mu, delta, or kappa opioid receptors. In 1988, Sibinga and Goldstein published the first review that addressed whether cells from the immune system express opioid receptors. The criteria that they used, namely, structure-activity relationships, stereoselectivity, dose- and concentration-dependence, and saturability are still relevant criteria today for determining if an immunological response is mediated by either the mu, delta or kappa opioid receptors. Radioligand receptor binding studies and functional studies that clearly show the presence of an opioid receptor on immunocytes are presented. Selective agonists and antagonists for the mu, delta, and kappa opioid receptors are discussed, and the need for their use in experiments is emphasized. Conditions used in functional assays are very important. Receptor desensitization and downregulation occur within minutes after the application of an agonist. However, many immunological assays are applying an agonist for days before measuring an immunological effect. The results obtained may reflect changes that are results of receptor desensitization and/or downregulation instead of changes that are observed with acute activation of the receptor. The future of receptor pharmacology lies in the crosstalk and dimerization of G protein-coupled receptors. In transfected systems, opioid receptors have been shown to dimerize with chemokine and cannabinoid receptors, resulting in crosstalk between different types of receptors.