Facilitation of μ-Opioid Receptor Activity by Preventing δ-Opioid Receptor-Mediated Codegradation

被引：184

作者：

He, Shao-Qiu ^{[2
,3
]}

Zhang, Zhen-Ning ^{[1
]}

Guan, Ji-Song ^{[2
,3
]}

Liu, Hong-Rui ^{[1
]}

Zhao, Bo ^{[2
,3
]}

Wang, Hai-Bo ^{[1
,2
,3
]}

Li, Qian ^{[1
]}

Yang, Hong ^{[2
,3
]}

Luo, Jie ^{[1
]}

Li, Zi-Yan ^{[1
]}

Wang, Qiong ^{[1
]}

Lu, Ying-Jin ^{[2
,3
]}

Bao, Lan ^{[1
]}

Zhang, Xu ^{[2
,3
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China

[3] Chinese Acad Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China

来源：

NEURON | 2011年 / 69卷 / 01期

基金：

中国国家自然科学基金;

关键词：

DORSAL-ROOT GANGLIA; PROTEIN-COUPLED RECEPTORS; NOXIOUS THERMAL STIMULI; RAT SPINAL-CORD; KNOCK-OUT MICE; DOWN-REGULATION; PHYSICAL-DEPENDENCE; MORPHINE ANALGESIA; SUBSTANCE-P; TOLERANCE;

D O I：

10.1016/j.neuron.2010.12.001

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

delta-opioid receptors (DORs) form heteromers with mu-opioid receptors (MORs) and negatively regulate MOR-mediated spinal analgesia. However, the underlying mechanism remains largely unclear. The present study shows that the activity of MORs can be enhanced by preventing MORs from DOR-mediated codegradation. Treatment with DOR-specific agonists led to endocytosis of both DORs and MORs. These receptors were further processed for ubiquitination and lysosomal degradation, resulting in a reduction of surface MORs. Such effects were attenuated by treatment with an interfering peptide containing the first transmembrane domain of MOR (MORTm1), which interacted with DORs and disrupted the MOR/DOR interaction. Furthermore, the systemically applied fusion protein consisting of MORTM1 and TAT at the C terminus could disrupt the MOR/DOR interaction in the mouse spinal cord, enhance the morphine analgesia, and reduce the antinociceptive tolerance to morphine. Thus, dissociation of MORs from DORs in the cell membrane is a potential strategy to improve opioid analgesic therapies.

引用

页码：120 / 131

页数：12

共 55 条

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