The Agonist of Adenosine A1 Receptor Induced Desensitization of delta Opioid receptor-mediated Raf-1/MEK/ERK Signaling by Feedback Phosphorylation of Raf-1-Ser289/296/301
文献类型：期刊论文
| 作者 | Xu, Chi1,2; Cheng, Yun3; Han, Manman4; Tao, Yimin3; Liu, Jing-Gen1,2,3,4
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| 刊名 | NEUROCHEMICAL RESEARCH
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| 出版日期 | 2022-12-16 |
| 页码 | 12 |
| 关键词 | Adenosine A1 receptor N6-cyclohexyladenosine Delta opioid receptor Raf-1 Desensitization |
| ISSN号 | 0364-3190 |
| DOI | 10.1007/s11064-022-03843-2 |
| 通讯作者 | Xu, Chi(xuchi@zcmu.edu.cn) ; Liu, Jing-Gen(jgliu@simm.ac.cn) |
| 英文摘要 | Our previous study found that activation of adenosine A1 receptor (A(1)R) induced phosphorylation of delta opioid receptor (DOR) and desensitization of its downstream signaling molecules, cAMP and Akt. To further investigate the effect of A(1)R agonist on DOR signaling and the underlying mechanism, we examined the effect of A(1)R activation upon binding of its agonist N6-cyclohexyl-adenosine (CHA) on DOR-mediated Raf-1/MEK/ERK activation, and found that prolonged CHA exposure resulted in downregulation of DOR-mediated Raf-1/MEK/ERK signaling pathway. CHA-treatment time dependently attenuated Raf-1-Ser338 phosphorylation induced by [D-Pen2,5] enkephalin (DPDPE), a specific agonist of DOR, and further caused downregulation of the Raf-1/MEK/ERK signaling pathway activated by DOR agonist. Moreover, CHA exposure time-dependently induced the phosphorylation of Raf-1-Ser289/296/301, the inhibitory phosphorylation sites that were regulated by negative feedback, thereby inhibiting activation of the MEK/ERK pathway, and this effect could be blocked by MEK inhibitor U0126. Finally, we proved that the heterologous desensitization of the Raf-1/MEK/ERK cascade was essential in the regulation of anti-nociceptive effect of DOR agonists by confirming that such effect was inhibited by pretreatment of CHA. Therefore, we conclude that the activation of A(1)R inhibits DOR-mediated MAPK signaling pathway via heterologous desensitization of the Raf-1/MEK/ERK cascade, which is a result of ERK-mediated Raf-1-Ser289/296/301 phosphorylation mediated by activation of A(1)R. |
| WOS关键词 | ADENOSINE RECEPTOR ; 14-3-3 BINDING ; RAF-1 ; ACTIVATION ; RAT ; IDENTIFICATION ; NEUROGENESIS ; ROLES |
| 资助项目 | Zhejiang Provincial Natural Science Foundation of China[LY22H270004] ; Zhejiang Chinese Medical University[2020ZG53] ; National Natural Science Foundation of China[82030112] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000899911300001 |
| 出版者 | SPRINGER/PLENUM PUBLISHERS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304264]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Chi; Liu, Jing-Gen |
| 作者单位 | 1.Zhejiang Chinese Med Univ, Affiliated Hosp 3, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurol Zhejiang Prov, Hangzhou 310053, Peoples R China 2.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Key Lab Neuropharmacol & Translat Med Zhejiang Pro, Hangzhou 310053, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai, Peoples R China 4.Zhejiang Chinese Med Univ, Sch Pharm, Hangzhou 310053, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Chi,Cheng, Yun,Han, Manman,et al. The Agonist of Adenosine A1 Receptor Induced Desensitization of delta Opioid receptor-mediated Raf-1/MEK/ERK Signaling by Feedback Phosphorylation of Raf-1-Ser289/296/301[J]. NEUROCHEMICAL RESEARCH,2022:12. |
| APA | Xu, Chi,Cheng, Yun,Han, Manman,Tao, Yimin,&Liu, Jing-Gen.(2022).The Agonist of Adenosine A1 Receptor Induced Desensitization of delta Opioid receptor-mediated Raf-1/MEK/ERK Signaling by Feedback Phosphorylation of Raf-1-Ser289/296/301.NEUROCHEMICAL RESEARCH,12. |
| MLA | Xu, Chi,et al."The Agonist of Adenosine A1 Receptor Induced Desensitization of delta Opioid receptor-mediated Raf-1/MEK/ERK Signaling by Feedback Phosphorylation of Raf-1-Ser289/296/301".NEUROCHEMICAL RESEARCH (2022):12. |
入库方式： OAI收割
来源：上海药物研究所
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