Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia

	Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia
	Guan, JS; Xu, ZZ; Gao, H; He, SQ; Ma, GQ; Sun, T; Wang, LH; Zhang, ZN; Lena, I; Kitchen, I
刊名	CELL
	2005
卷号	122 期号:4 页码:619-631
通讯作者	Zhang, X (reprint author), Chinese Acad Sci, Inst Neurosci, Key Lab Neurobiol, Shanghai 200031, Peoples R China.,xu.zhang@ion.ac.cn
英文摘要	Opioid and tachykinin systems are involved in modulation of pain transmission in the spinal cord. Regulation of surface opioid receptors on nociceptive afferents is critical for opioid analgesia. Plasma-membrane insertion of delta-opioid receptors (DORs) is induced by stimulus-triggered exocytosis of DOR-containing large dense-core vesicles (LDCVs), but how DORs become sorted into the regulated secretory pathway is unknown. Here we report that direct interaction between protachykinin and DOR is responsible for sorting of DORs into LDCVs, allowing stimulus-induced surface insertion of DORs and DOR-mediated spinal analgesia. This interaction is mediated by the substance P domain of protachykinin and the third luminal domain of DOR. Furthermore, deletion of the preprotachykinin A gene reduced stimulus-induced surface insertion of DORs and abolished DOR-mediated spinal analgesia and morphine tolerance. Thus, protachylkinin is essential for modulation of the sensitivity of nociceptive afferents to opioids, and the opioid and tachykinin systems are directly linked by protachykinin/DOR interaction.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	SECRETORY GRANULE BIOGENESIS ; PROTEIN-COUPLED RECEPTOR ; ROOT GANGLION NEURONS ; RAT SPINAL-CORD ; SUBSTANCE-P ; PHARMACOLOGICAL CHARACTERIZATION ; PHYSICAL-DEPENDENCE ; PERIPHERAL AXOTOMY ; KNOCKOUT MICE ; MU
收录类别	SCI
语种	英语
WOS记录号	WOS:000231555100016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1888]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Guan, JS,Xu, ZZ,Gao, H,et al. Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia[J]. CELL,2005,122(4):619-631.
APA	Guan, JS.,Xu, ZZ.,Gao, H.,He, SQ.,Ma, GQ.,...&Zhang, X.(2005).Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia.CELL,122(4),619-631.
MLA	Guan, JS,et al."Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia".CELL 122.4(2005):619-631.