Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Centre of Membrane Proteins and Receptors, University of Birmingham and University of Nottingham, Midlands NG7 2UH, UK.
Cells. 2020 Nov 2;9(11):2400. doi: 10.3390/cells9112400.
Understanding the link between agonist-induced phosphorylation of the mu-opioid receptor (MOR) and the associated physiological effects is critical for the development of novel analgesic drugs and is particularly important for understanding the mechanisms responsible for opioid-induced tolerance and addiction. The family of G protein receptor kinases (GRKs) play a pivotal role in such processes, mediating phosphorylation of residues at the C-tail of opioid receptors. Numerous strategies, such as phosphosite specific antibodies and mass spectrometry have allowed the detection of phosphorylated residues and the use of mutant knock-in mice have shed light on the role of GRK regulation in opioid receptor physiology. Here we review our current understanding on the role of GRKs in the actions of opioid receptors, with a particular focus on the MOR, the target of most commonly used opioid analgesics such as morphine or fentanyl.
了解 μ 阿片受体（MOR）激动剂诱导的磷酸化与其相关生理效应之间的联系对于新型镇痛药物的开发至关重要，对于理解导致阿片类药物耐受和成瘾的机制尤为重要。G 蛋白受体激酶（GRK）家族在这些过程中起着关键作用，介导阿片受体 C 末端残基的磷酸化。许多策略，如磷酸化特异性抗体和质谱分析，已经允许检测磷酸化残基的存在，而突变敲入小鼠的使用则揭示了 GRK 调节在阿片受体生理学中的作用。在这里，我们回顾了我们目前对 GRK 在阿片受体作用中的作用的理解，特别是对 MOR 的理解，MOR 是大多数常用阿片类镇痛药（如吗啡或芬太尼）的作用靶点。
