PKA and ERK1/2 are involved in dopamine D₁ receptor-induced heterologous desensitization of the δ opioid receptor.
PKA and ERK1/2 are involved in dopamine D₁ receptor-induced heterologous desensitization of the δ opioid receptor.
复制标题
PKA 和 ERK1/2 参与多巴胺 Dα 受体诱导的 δ 阿片受体异源脱敏。
DOI：
10.1016/j.lfs.2013.04.006
复制
发表时间：
2013
期刊：
影响因子：
6.1
通讯作者：
Liu-Chen,Lee-Yuan
中科院分区：
文献类型：
--
作者：
Xu,Wei;Chen,Chongguang;Li,Jian-Guo;Dimattio,Kelly;Wang,Yujun;Unterwald,Ellen;Liu-Chen,Lee-Yuan
目的：慢性给予可卡因可减弱纹状体内的阿片受体信号，其脱敏作用是通过可卡因对多巴胺D1R的间接作用实现的。此外，DOPR和D1R在一些大鼠纹状体神经元中共存。本研究以稳定表达HA-大鼠D1R(HA-D1R)的MAIN METHODSNG 108-15细胞和稳定表达标志鼠DOPR(FLAG-DOPR)和HA-D1R的中国仓鼠卵巢(CHO)细胞为细胞模型，探讨D1R激活DOPR脱敏的机制。受体结合、[35S]GTPγS结合、受体磷酸化和蛋白印迹检测γ的亲和力、表达、内化、下调、脱敏、磷酸化和磷酸化ERK1/2。分别用DOPR激动剂DPDPE和D1R激动剂SKF-82958预先处理30min，减弱DPDPE刺激的[35S]GTP DOPR S与G蛋白的结合，显示DOPR的同源和异源脱敏。SKF-82958不影响DOPR受体拮抗剂或激动剂的亲和力，也不诱导DOPR在CHO-FLAG-DOPR/HA-D1R细胞中的磷酸化、内化或下调。用PKA、MEK1和PI3K抑制剂(而不是PKC)预处理细胞，可减弱SKF-82958诱导的DOPR脱敏。D1R激动剂SKF-82958促进ERK1/2的磷酸化，用MEK1和PI3K抑制剂预处理可降低这种作用，但不影响PKA和PKC的作用。这些结果表明，D1R诱导的DOPR异源脱敏与ERK1/2和/或PKA的激活有关，而与PKC无关。本研究提供了D1R激活诱导DOPR脱敏的可能机制。
AIMSChronic administration of cocaine attenuates delta opioid receptor (DOPR) signaling in the striatum and the desensitization is mediated by the indirect actions of cocaine on dopamine D1receptors (D1R). In addition, DOPR and D1R co-exist in some rat striatal neurons. In the present study, we examined the underlying mechanism of DOPR desensitization by D1R activation.MAIN METHODSNG 108-15 cells stably expressing HA-rat D1receptor (HA-D1R) and Chinese hamster ovary (CHO) cells stably expressing both FLAG-mouse DOPR (FLAG-DOPR) and HA-D1R were used as the cell models. Receptor binding, [35S]GTPγS binding, receptor phosphorylation and western blot were conducted to examine DOPR affinity, expression, internalization, downregulation, desensitization, phosphorylation and phosphorylated ERK1/2.KEY FINDINGSPretreatment with either the DOPR agonist DPDPE or the D1R agonist SKF-82958 for 30min attenuated DPDPE-stimulated [35S]GTPγS binding to G proteins, demonstrating homologous and heterologous desensitization of the DOPR, respectively. SKF-82958 pretreatment did not affect the level of DOPR or affinity of DOPR antagonist or agonists, nor did it induce phosphorylation, internalization or down-regulation of the DOPR in the CHO-FLAG-DOPR/HA-D1R cells. Pretreatment of cells with inhibitors of PKA, MEK1 and PI3K, but not PKC, attenuated SKF-82958-induced desensitization of the DOPR. The D1R agonist SKF-82958 enhanced phosphorylation of ERK1/2, and pretreatment with inhibitors of MEK1 and PI3K, but not PKA and PKC, reduced the effect. These results indicate that activation of ERK1/2 and/or PKA, but not PKC, is involved in D1receptor-induced heterologous desensitization of the DOPR.SIGNIFICANCEThis study provides possible mechanisms underlying D1R activation-induced DOPR desensitization.
登录
查看更多内容
影响因子：
5.3
作者：
Hopf, FW;Mailliard, WS;Bonci, A
通讯作者：
Bonci, A
影响因子：
5
作者：
Chen, CG;Li, J;Liu-Chen, LY
通讯作者：
Liu-Chen, LY
DOI：
10.1016/j.molbrainres.2004.10.025
发表时间：
2005-02
期刊：
Brain research. Molecular brain research
影响因子：
--
作者：
S. Perrine;J. Schroeder;E. Unterwald
通讯作者：
S. Perrine;J. Schroeder;E. Unterwald
SH-SY5Y 人神经母细胞瘤细胞中毒蕈碱 M3 和 α1B 肾上腺素受体与 Gαq/11 的同源和异源解偶联
DOI：
--
发表时间：
2001
期刊：
影响因子：
--
作者：
R. Bundey;S. Nahorski
通讯作者：
S. Nahorski
体外暴露于去氧肾上腺素后，大鼠尾动脉收缩和磷酸肌醇积累的异源脱敏是由 Galphaq 和 Galphai 水平降低介导的。
DOI：
--
发表时间：
1997
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Seasholtz,TM;Gurdal,H;Wang,HY;Cai,G;Johnson,MD;Friedman,E
通讯作者：
Friedman,E