...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular pharmacology. >δ-opioid receptors stimulate the metabolic sensor AMP-activated protein kinase through coincident signaling with G q/11-coupled receptors
【24h】

δ-opioid receptors stimulate the metabolic sensor AMP-activated protein kinase through coincident signaling with G q/11-coupled receptors

机译：δ阿片受体通过与G q / 11偶联受体的同步信号刺激代谢传感器AMP激活的蛋白激酶

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

AMP-activated protein kinase (AMPK) and δ-opioid receptors (DORs) are both involved in controlling cell survival, energy metabolism, and food intake, but little is known on the interaction between these two signaling molecules. Here we show that activation of human DORs stably expressed in Chinese hamster ovary (CHO) cells increased AMPK activity and AMPK phosphorylation on Thr172. DOR-induced AMPK phosphorylation was prevented by pertussis toxin, reduced by protein kinase A (PKA) activators, and unaffected by PKA, transforming growth factor-β-activated kinase 1, mitogen-activated protein kinase, and protein kinase C inhibitors. Conversely, the DOR effect was reduced by Ca 2+/ calmodulin-dependent protein kinase kinase (CaMKK) inhibition, apyrase treatment, G q/11 antagonism, and blockade of P2 purinergic receptors. Apyrase treatment also depressed DOR stimulation of intracellular Ca 2+ concentration, whereas P2 receptor antagonism blocked DOR stimulation of inositol phosphate accumulation. In SH-SY5Y neuroblastoma cells and primary olfactory bulb neurons, DOR activation failed to affect AMPK phosphorylation per se but potentiated the stimulation by either muscarinic agonists or 2-methyl-thio-ADP. Sequestration of G protein βγ subunits (Gβγ) blocked the DOR potentiation of AMPK phosphorylation induced by oxotremorine-M. In CHO cells, the AMPK activator 5-aminoimidazole-4- carboxamide1-β-D-ribonucleoside stimulated AMPK phosphorylation and glucose uptake, whereas pharmacological inhibition of AMPK, expression of a dominantnegative mutant of AMPKα1, and P2Y receptor blockade reduced DOR-stimulated glucose uptake. The data indicate that in different cell systems, DOR activation up-regulates AMPK through a Gβγ- dependent synergistic interaction with G q/11-coupled receptors, potentiating Ca 2+ release and CaMKKβ-dependent AMPK phosphorylation. In CHO cells, this coincident signaling mechanism is involved in DOR-induced glucose uptake.
机译：AMP激活的蛋白激酶（AMPK）和δ阿片受体（DOR）均参与控制细胞存活，能量代谢和食物摄入，但对这两个信号分子之间的相互作用了解甚少。在这里，我们显示了在中国仓鼠卵巢（CHO）细胞中稳定表达的人类DOR的激活增加了Thr172上的AMPK活性和AMPK磷酸化。百日咳毒素可阻止DOR诱导的AMPK磷酸化，蛋白激酶A（PKA）激活剂可降低DOR诱导的AMPK磷酸化，而PKA则不影响DOR诱导的AMPK磷酸化，转化生长因子-β激活的激酶1，丝裂原激活的蛋白激酶和蛋白激酶C抑制剂。相反，Ca 2 + /钙调蛋白依赖性蛋白激酶激酶（CaMKK）抑制，腺苷三磷酸双磷酸酶处理，G q / 11拮抗作用和P2嘌呤能受体的阻滞降低了DOR的作用。 Apyrase处理还抑制了细胞内Ca 2+浓度的DOR刺激，而P2受体拮抗作用阻止了DOR刺激肌醇磷酸积累。在SH-SY5Y神经母细胞瘤细胞和原发性嗅球神经元中，DOR激活本身不能影响AMPK磷酸化，但可以增强毒蕈碱激动剂或2-甲基-硫代ADP的刺激作用。螯合G蛋白βγ亚基（Gβγ）阻断了由氧代苯甲酸-M诱导的AMPK磷酸化的DOR增强。在CHO细胞中，AMPK激活剂5-氨基咪唑-4-羧酰胺1-β-D-核糖核苷刺激AMPK磷酸化和葡萄糖摄取，而AMPK的药理抑制，AMPKα1显性负突变体的表达和P2Y受体阻滞降低了DOR刺激的葡萄糖摄取。数据表明，在不同的细胞系统中，DOR激活通过与G q / 11偶联受体的Gβγ依赖性协同相互作用上调AMPK，增强Ca 2+释放和CaMKKβ依赖性AMPK磷酸化。在CHO细胞中，这种一致的信号传导机制与DOR诱导的葡萄糖摄取有关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号