Facilitation of mu-Opioid Receptor Activity by Preventing delta-Opioid Receptor-Mediated Codegradation

CORC > 上海神经科学研究所 > 中国科学院上海生命科学研究院神经科学研究所 > 神经所(总)

	Facilitation of mu-Opioid Receptor Activity by Preventing delta-Opioid Receptor-Mediated Codegradation
	Zhang, Xu
刊名	NEURON
	2011
卷号	69 期号:1 页码:120-131
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
ISSN号	0896-6273
通讯作者	Bao, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China,baolan@sibs.ac.cn ; xu.zhang@ion.ac.cn
英文摘要	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 (MOR(Tm1)), which interacted with DORs and disrupted the MOR/DOR interaction. Furthermore, the systemically applied fusion protein consisting of MOR(TM1) 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.
学科主题	Neurosciences & Neurology
收录类别	SCI
资助信息	National Natural Science Foundation of China[30630029, 30621062]; National Basic Research Program of China[2009CB522005, 2010CB912000, 2011CBA00400, 2007CB914501]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1558]
专题	上海神经科学研究所_神经所(总) 上海神经科学研究所_感觉系统研究组
推荐引用方式 GB/T 7714	Zhang, Xu. Facilitation of mu-Opioid Receptor Activity by Preventing delta-Opioid Receptor-Mediated Codegradation[J]. NEURON,2011,69(1):120-131.
APA	Zhang, Xu.(2011).Facilitation of mu-Opioid Receptor Activity by Preventing delta-Opioid Receptor-Mediated Codegradation.NEURON,69(1),120-131.
MLA	Zhang, Xu."Facilitation of mu-Opioid Receptor Activity by Preventing delta-Opioid Receptor-Mediated Codegradation".NEURON 69.1(2011):120-131.