Binding affinity to and dependence on some opioids in Sf9 insect cells expressing human mu-opioid receptor

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Binding affinity to and dependence on some opioids in Sf9 insect cells expressing human mu-opioid receptor
	Liu, ZH ; He, Y ; Jin, WQ ; Chen, XJ ; Zhang, HP ; Shen, QX ; Chi, ZQ
刊名	ACTA PHARMACOLOGICA SINICA
	2003-09
卷号	24 期号:9 页码:859-863
关键词	narcotics mu opioid receptor competitive binding cyclic AMP analgesia opioid-related disorders
ISSN号	1671-4083
文献子类	Article
英文摘要	AIM: To investigate the receptor binding affinity and naloxone-precipitated cAMP overshoot of dihydroetorphine, fentanyl, heroin, and pethidine in Sf9 insect cells expressing human mu-opioid receptor (Sf9-mu cells). METHODS: Competitive binding assay of [(3)H]ohmefentanyl was used to reveal the affinity for p-opioid receptor in Sf9-mu cells. [(3)H]cAMP RIA was used to determine cAMP level. Antinociceptive activity was evaluated using 55 degreesC mouse hot plate test. Naloxone-precipitated withdrawal jumping was used to reflect physical dependence in mice. RESULTS: All drugs displayed antinociceptive activity and produced physical dependence in mice. The K(i) values of dihydroetorphine, fentanyl, heroin, and pethidine in competitive binding assay were (0.85 +/- 0.20) nmol, (59.1 +/- 11.7) nmol, (0.36 +/- 0.13) mumol, and (12.2 +/- 3.8) mumol respectively. The binding affinities of these drugs for mu-opioid receptor in Sf9-mu cells were paralleled to their antinociceptive activities in mice. After chronic pretreatment with these drugs, naloxone induced cAMP withdrawal overshoot in Sf9-mu cells. The dependence index in Sf9-mu cells was calculated as K(i) value in competitive binding assay over EC(50) value in naloxone-precipitated cAMP assay. The physical dependence index in mice was calculated as antinociceptive ED(50)/withdrawal jumping cumulative ED(50). There was a good linear correlation between dependence index in Sf9-mu cells and physical dependence index in mice. CONCLUSION: The Sf9-mu cells could be used as a cell model to evaluate the receptor binding affinity and physical dependent liability of analgesic agents.
WOS关键词	OHMEFENTANYL ; MICE ; WITHDRAWAL ; PROTEINS ; GENE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:942076
出版者	SHANGHAI INST MATERIA MEDICA
WOS记录号	WOS:000185357500004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274188]
专题	药理学第一研究室
通讯作者	Jin, WQ
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Shanghai Inst Planned Parenthood Res, Shanghai 200032, Peoples R China
推荐引用方式 GB/T 7714	Liu, ZH,He, Y,Jin, WQ,et al. Binding affinity to and dependence on some opioids in Sf9 insect cells expressing human mu-opioid receptor[J]. ACTA PHARMACOLOGICA SINICA,2003,24(9):859-863.
APA	Liu, ZH.,He, Y.,Jin, WQ.,Chen, XJ.,Zhang, HP.,...&Chi, ZQ.(2003).Binding affinity to and dependence on some opioids in Sf9 insect cells expressing human mu-opioid receptor.ACTA PHARMACOLOGICA SINICA,24(9),859-863.
MLA	Liu, ZH,et al."Binding affinity to and dependence on some opioids in Sf9 insect cells expressing human mu-opioid receptor".ACTA PHARMACOLOGICA SINICA 24.9(2003):859-863.