Adenosine A(1) receptor agonist N-6-cyclohexyladenosine induced phosphorylation of delta oploid receptor and desensitization of its signaling opioid
文献类型：期刊论文
| 作者 | Cheng, Yun1; Tao, Yi-min1; Sun, Jian-feng1; Wang, Yu-hua1,2; Xu, Xue-jun1; Chen, Jie1; Chi, Zhi-qiang1 ; Liu, Jing-gen1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 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. |
| WOS关键词 | ADENYLYL-CYCLASE ACTIVITY ; G-PROTEIN ACTIVATION ; HETEROLOGOUS DESENSITIZATION ; DOWN-REGULATION ; CROSS-TALK ; INTERNALIZATION ; CELLS ; TOLERANCE ; MU ; ANTINOCICEPTION |
| 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研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3893613 |
| WOS记录号 | WOS:000279538400003 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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