School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
Br J Pharmacol. 2011 Sep;164(2):294-7. doi: 10.1111/j.1476-5381.2011.01387.x.
The link between µ-opioid receptor phosphorylation and function is of critical importance to our understanding of the mechanisms underlying tolerance to opioid drugs. Increasingly sophisticated techniques are needed to assess the phosphorylation status of GPCRs, such as the use of phosphosite-specific antibodies that can monitor the kinetics of phosphorylation and dephosphorylation of individual residues in a receptor. Here the use of phosphosite-specific antibodies, raised against phosphorylated residues in the COOH-terminus of the µ-opioid receptor is discussed, along with some of the important findings that this approach has so far revealed. These include the finding that the µ-opioid receptor is constitutively phosphorylated, and that upon agonist removal it undergoes dephosphorylation equally well whether it is at the cell surface or internalized in endosomes. Thus already these phosphosite-specific antibodies are providing important new information about µ-opioid receptor function and the actions of opioid drugs.
This article is a commentary on Doll et al., pp. 298-307 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01382.x.
µ-阿片受体磷酸化与功能之间的联系对于我们理解阿片类药物耐受的机制至关重要。需要越来越复杂的技术来评估 GPCR 的磷酸化状态，例如使用磷酸化特异性抗体，可以监测受体中单个残基的磷酸化和去磷酸化动力学。本文讨论了针对 µ-阿片受体羧基末端磷酸化残基的磷酸化特异性抗体的使用，并介绍了该方法迄今为止揭示的一些重要发现。这些发现包括 µ-阿片受体是组成性磷酸化的，并且在激动剂去除后，无论它是在细胞表面还是内化在内体中，都能同样好地进行去磷酸化。因此，这些磷酸化特异性抗体已经为 µ-阿片受体功能和阿片类药物的作用提供了重要的新信息。
本文是对 Doll 等人在本期杂志第 298-307 页上的评论。要查看本文，请访问 http://dx.doi.org/10.1111/j.1476-5381.2011.01382.x。
