Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid

doi:10.1038/aps.2010.70

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	Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid
	Cheng, Yun 1; Tao, Yi-min 1; Sun, Jian-feng 1; Wang, Yu-hua 1,2; Xu, Xue-jun 1; Chen, Jie 1; Chi, Zhi-qiang1 ; Liu, Jing-gen1
刊名	ACTA PHARMACOLOGICA SINICA
	2010-07
卷号	31 期号:7 页码:784-790
关键词	adenosine A(1) receptor N-6-cyclohexyladenosine delta opioid receptor cAMP Akt
ISSN号	1671-4083
DOI	10.1038/aps.2010.70
文献子类	Article
英文摘要	Aim: To define the effect of adenosine A(1) receptor (A(1)R) on delta opioid receptor (DOR)-mediated signal transduction. Methods: CHO cells stably expressing HA-tagged A(1)R and DOR-CFP fusion protein were used. The localization of receptors was observed using confocal microscope. DOR-mediated inhibition of adenylyl cyclase was measured using cyclic AMP assay. Western blots were employed to detect the phosphorylation of Akt and the DOR. The effect of A(1)R agonist N-6-cyclohexyladenosine (CHA) on DOR down-regulation was assessed using radioligand binding assay. Results: CHA 1 mu mol/L time-dependently attenuated DOR agonist [D-Pen(2,5)] enkephalin (DPDPE)-induced inhibition of intracellular cAMP accumulation with a t(1/2)=2.56 (2.09-3.31) h. Pretreatment with 1 mu mol/L CHA for 24 h caused a right shift of the dose-response curve of DPDPE-mediated inhibition of cAMP accumulation, with a significant increase in EC50 but no change in E-max. Pretreatment with 1 mu mol/L CHA for 1 h also induced a significant attenuation of DPDPE-stimulated phosphorylation of Akt. Moreover, CHA time-dependently phosphorylated DOR (Ser363), and this effect was inhibited by A(1)R antagonist 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) but not by DOR antagonist naloxone. However, CHA failed to produce the down-regulation of DOR, as neither receptor affinity (K-d) nor receptor density (B-max) of DOR showed significant change after chronic CHA exposure. Conclusion: Activation of A(1)R by its agonist caused heterologous desensitization of DOR-mediated inhibition of intracellular cAMP accumulation and phosphorylation of Akt. Activation of A(1)R by its agonist also induced heterologous phosphorylation but not down-regulation of DOR.
资助项目	Ministry of Science and Technology of China[G2003CB515400] ; Ministry of Science and Technology of China[2009CB522000] ; National Natural Science Foundation of China[30425002] ; Chinese Academy of Sciences[KSCXI/YW/R/68]
WOS关键词	ADENYLYL-CYCLASE ACTIVITY ; G-PROTEIN ACTIVATION ; HETEROLOGOUS DESENSITIZATION ; DOWN-REGULATION ; CROSS-TALK ; INTERNALIZATION ; CELLS ; TOLERANCE ; MU ; ANTINOCICEPTION
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3893613
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000279538400003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278841]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jing-gen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210046, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Yun,Tao, Yi-min,Sun, Jian-feng,et al. Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid[J]. ACTA PHARMACOLOGICA SINICA,2010,31(7):784-790.
APA	Cheng, Yun.,Tao, Yi-min.,Sun, Jian-feng.,Wang, Yu-hua.,Xu, Xue-jun.,...&Liu, Jing-gen.(2010).Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid.ACTA PHARMACOLOGICA SINICA,31(7),784-790.
MLA	Cheng, Yun,et al."Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid".ACTA PHARMACOLOGICA SINICA 31.7(2010):784-790.