μ opioid receptor carboxyl terminal-derived peptide alleviates morphine tolerance by inhibiting β-arrestin2

Author:

Zhang Meng1,Zhang Yanling1,Li Jian2,Li Junliang2,Ji Junwei2,Wang Zhongshan2

Affiliation:

1. Department of Gynecology, Central Hospital of Xuzhou, Affiliated Hospital of Southeast University

2. Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, China

Abstract

The interaction between the μ opioid receptor (MOR) and β-arrestin2 serves as a model for addressing morphine tolerance. A peptide was designed to alleviate morphine tolerance through interfering with the interaction of MOR and β-arrestin2. We developed a peptide derived from MOR. The MOR-TAT-pep peptide was expressed in E. coli Bl21(DE3) and purified. The effects of MOR-TAT-pep in alleviating morphine tolerance was examined through behavior tests. The potential mechanism was detected by Western blotting, Mammalian Two-Hybrid and other techniques. The pretreatment with MOR-TAT-pep prior to morphine usage led to an enhanced analgesic effectiveness of morphine and a significant reduction in the development of morphine tolerance. The peptide directly interacted with β-arrestin2 during morphine treatment and deceased the membrane recruitment of β-arrestin2. MOR-TAT-pep effectively suppressed the increase of β-arrestin2 induced by morphine. The MOR-TAT-pep could alleviate morphine tolerance through inhibition of β-arrestin2.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

General Neuroscience

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