Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP-response element binding protein in cultured rat hippocampal neurons

	Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP-response element binding protein in cultured rat hippocampal neurons
	Gao, C ; Chen, LW ; Tao, YM ; Chen, J; Xu, XJ ; Chi, ZQ
刊名	ACTA PHARMACOLOGICA SINICA
	2003-12
卷号	24 期号:12 页码:1253-1258
关键词	ohmefentanyl stereoisomers cAMP-response element binding protein mu opioid receptor cyclic AMP hippocampal neurons phosphorylation
ISSN号	1671-4083
文献子类	Article
英文摘要	AIM: To define the effects and signal pathways of ohmefentanyl stereoisomers [(-)-cis-(3R,4S,2'R) OMF (F9202), (+)-cis-(3R,4S,2'S) OMF (F9204), and (-)-cis-(3S,4S,2'R) OMF (F9203)] on the phosphorylation of cAMP-response element binding protein (CREB) in cultured rat hippocampal neurons. METHODS: The effects of the three OMF stereoisomers and morphine (Mor) on cAMP accumulation and CREB phosphorylation were monitored by radioimmunoassay and Western blot analysis, respectively. RESULTS: The three OMF stereoisomers and Mor could all partially inhibit forskolin-stimulated (25 mumol/L, 15 min) cAMP accumulation in a dose-dependent manner and this effect could be reversed by naloxone. F9202, F9204, and Mor could significantly increase CREB phosphorylation from 2.88 to 3.59 folds over control levels after 30-min exposure. This effect was reversed by naloxone, but F9203 failed to increase CREB phosphorylation. KN-62 and staurosporine significantly blocked the opioids-induced CREB phosphorylation, while H-89 and PD 98059 had no effect on the actions. CONCLUSION: Mor, F9202, and F9204, which could induce psychological dependence affected via the p-opioid receptor, stimulated intracellular signal pathways involving Ca2+/calmodulin-dependent protein kinases (CCDPK) and protein kinase C (PKC) pathways, which in turn initiated CREB phosphorylation. F9203, which could not induce dependence, had no effect on CREB phosphorylation in hippocampal neurons. The increased CREB phosphorylation in hippocampal neurons may play a role in opioids dependence.
WOS关键词	CREB PHOSPHORYLATION ; ANALGESIC ACTIVITY ; OPIOID RECEPTORS ; MICE ; ADDICTION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:1270661
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000187218600013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274151]
专题	院士及顾问专家
通讯作者	Chi, ZQ
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Gao, C,Chen, LW,Tao, YM,et al. Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP-response element binding protein in cultured rat hippocampal neurons[J]. ACTA PHARMACOLOGICA SINICA,2003,24(12):1253-1258.
APA	Gao, C,Chen, LW,Tao, YM,Chen, J,Xu, XJ,&Chi, ZQ.(2003).Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP-response element binding protein in cultured rat hippocampal neurons.ACTA PHARMACOLOGICA SINICA,24(12),1253-1258.
MLA	Gao, C,et al."Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP-response element binding protein in cultured rat hippocampal neurons".ACTA PHARMACOLOGICA SINICA 24.12(2003):1253-1258.