Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Int J Mol Sci. 2021 Apr 6;22(7):3779. doi: 10.3390/ijms22073779.
There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous opioid peptides act through opioid receptors, including mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR), and play important roles not only in analgesia, but also many other biological processes such as reward, stress response, feeding and emotion. The MOR gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple splice variants or isoforms. One type of these splice variants, the full-length 7 transmembrane (TM) Carboxyl ()-terminal variants, has the same receptor structures but contains different intracellular -terminal tails. The pharmacological functions of several endogenous opioid peptides through the mouse, rat and human OPRM1 7TM -terminal variants have been considerably investigated together with various mu opioid ligands. The current review focuses on the studies of these endogenous opioid peptides and summarizes the results from early pharmacological studies, including receptor binding affinity and G protein activation, and recent studies of β-arrestin2 recruitment and biased signaling, aiming to provide new insights into the mechanisms and functions of endogenous opioid peptides, which are mediated through the OPRM1 7TM -terminal splice variants.
存在三种主要的内源性阿片肽，脑啡肽、强啡肽和β-内啡肽，它们均来源于其前体。这些内源性阿片肽通过阿片受体发挥作用，包括μ阿片受体（MOR）、δ阿片受体（DOR）和κ阿片受体（KOR），它们不仅在镇痛中发挥重要作用，而且在许多其他生物学过程中也发挥着重要作用，如奖赏、应激反应、摄食和情绪。MOR 基因，OPRM1，经历广泛的选择性前体 mRNA 剪接，产生多种剪接变体或同工型。这些剪接变体中的一种，全长 7 跨膜（TM）羧基（C）-末端变体，具有相同的受体结构，但含有不同的细胞内 C-末端尾部。几种内源性阿片肽通过小鼠、大鼠和人 OPRM1 7TM-末端变体的药理学功能已与各种μ阿片配体一起进行了相当多的研究。本综述重点介绍了这些内源性阿片肽的研究，并总结了早期药理学研究的结果，包括受体结合亲和力和 G 蛋白激活，以及最近关于β-arrestin2 募集和偏向信号转导的研究，旨在为内源性阿片肽通过 OPRM1 7TM-末端剪接变体介导的机制和功能提供新的见解。
