Chinese scientists study new achievements

On January 13th, the American Neuron published the research results of the research team led by Zhang Xu, a member of the Institute of Neurosciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and the researcher Bao Yu, a researcher in the Institute of Biochemistry and Cell Biology. - "Facilitation of μ-opioid receptor activity by preventing δ-opioid receptor-mediated co-degradation".

Morphine and other opioids are currently the most effective analgesics, but they are susceptible to side effects such as toleration and dependence. The opioid peptides and their receptors in the spinal cord constitute an inhibitor system of pain modulation, wherein the μ opioid receptor mediates the effects of morphine and other analgesics, and the δ opioid receptor mediates the effects of endogenous enkephalin. Previous studies have suggested that δ opioid receptors can form heteromultimers with μ opioid receptors and negatively regulate μ opioid receptor-mediated analgesia. However, people still know little about the mechanisms involved.

The authors have found through a series of experiments that blocking opioid receptors entering the delta opioid receptor-mediated receptor degradation pathway can enhance μ opioid receptor-mediated analgesic efficacy. Under the stimulation of δ opioid receptor-specific agonists, the δ opioid receptors and μ opioid receptors located on the cell membrane are co-transformed into cells and enter the lysosomes for degradation. They also found that the first transmembrane segment of the μ opioid receptor mediates its binding to the δ opioid receptor, and therefore designed the TAT peptide that will help the macromolecule to penetrate the membrane and that it will be connected to the μ opioid receptor for the first time. Segment C interfering proteins are used to relieve the interaction between two opioid receptors in the spinal cord pain pathway. Animal experiments show that the injection of the interfering protein can hinder the interaction between the δ opioid receptor and the μ opioid receptor in the spinal cord, not only improves the analgesic effect of morphine, but also reduces the tolerance of morphine. These results suggest that activation of δ opioid receptors may result in the co-invasion and degradation of two types of opioid receptors, and this mechanism plays an important regulatory role in the desensitization of μ opioid receptors. The results of this study provide a new strategy for improving the analgesic effect of opioid analgesics.

This achievement was jointly completed by neurosurgical graduate students He Shaoqiu, Guan Jisong, and graduate student Zhang Zhenning of the Biochemical Cell Institute.

The work was funded by the Chinese Academy of Sciences, the 973 Program of the Ministry of Science and Technology, and the National Natural Science Foundation.