Peripheral pain is enhanced by insulin-like growth factor 1 through a G protein-mediated stimulation of T-type calcium channels
文献类型：期刊论文
| 作者 | Zhang, Y ; Qin, WJ ; Qian, ZY ; Liu, XJ ; Wang, H ; Gong, S ; Sun, YG ; Snutch, TP ; Jiang, XH ; Tao, J |
| 刊名 | SCIENCE SIGNALING
 |
| 出版日期 | 2014 |
| 卷号 | 7期号:346页码:94-94 |
| 关键词 | ROOT GANGLION NEURONS KINASE-C SENSORY NEURONS CA2+ CHANNELS IGF-I INSULIN-LIKE-GROWTH-FACTOR-1 RECEPTOR DOWN-REGULATION RAT MODULATION ACTIVATION |
| ISSN号 | 1945-0877 |
| 通讯作者 | Sun, YG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China.,yangang.sun@ion.ac.cn ; taoj@suda.edu.cn |
| 英文摘要 | Insulin-like growth factor 1 (IGF-1) is implicated in the nociceptive (pain) sensitivity of primary afferent neurons. We found that the IGF-1 receptor (IGF-1R) functionally stimulated voltage-gated T-type Ca2+ (Ca(V)3) channels in mouse dorsal root ganglia (DRG) neurons through a mechanism dependent on heterotrimeric G protein (heterotrimeric guanine nucleotide-binding protein) signaling. IGF-1 increased T-type channel currents in small-diameter DRG neurons in a manner dependent on IGF-1 concentration and IGF-1R but independent of phosphatidylinositol 3-kinase (PI3K). The intracellular subunit of IGF-1R coimmunoprecipitated with G(alpha o). Blocking G protein signaling by the intracellular application of guanosine diphosphate (GDP)-beta-S or with pertussis toxin abolished the stimulatory effects of IGF-1. Antagonists of protein kinase C alpha (PKC alpha), but not of PKC beta, abolished the IGF-1-induced T-type channel current increase. Application of IGF-1 increased membrane abundance of PKC alpha, and PKC alpha inhibition (either pharmacologically or genetically) abolished the increase in T-type channel currents stimulated by IGF-1. IGF-1 increased action potential firing in DRG neurons and increased the sensitivity of mice to both thermal and mechanical stimuli applied to the hindpaw, both of which were attenuated by intraplantar injection of a T-type channel inhibitor. Furthermore, inhibiting IGF-1R signaling or knocking down Ca(V)3.2 or PKC alpha in DRG neurons abolished the increased mechanical and thermal sensitivity that mice exhibited under conditions modeling chronic hindpaw inflammation. Together, our results showed that IGF-1 enhances T-type channel currents through the activation of IGF-1R that is coupled to a G protein-dependent PKC alpha pathway, thereby increasing the excitability of DRG neurons and the sensitivity to pain. |
| 学科主题 | Biochemistry & Molecular Biology ; Cell Biology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China [31371122, 81171056, 31271258, 81322015, 81200852]; National Natural Science Foundation of China (NSFC)-National Center for Scientific Research (CNRS) Joint Program [81311130114]; Natural Science Funding of Jiangsu Province [BK2011293]; Natural Science Funding for Colleges and Universities in Jiangsu Province [10KJB310013, 12KJB320010]; Scientific Research Foundation for the Returned Overseas Chinese Scholars of State Education Ministry; Priority Academic Program Development of Jiangsu Higher Education Institutions; Canadian Institutes of Health Research [10677]; Canada Research Chair in Neurobiology and Genomics-Biotechnology |
| 语种 | 英语 |
| 公开日期 | 2014-12-15 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/2639]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Zhang, Y,Qin, WJ,Qian, ZY,et al. Peripheral pain is enhanced by insulin-like growth factor 1 through a G protein-mediated stimulation of T-type calcium channels[J]. SCIENCE SIGNALING,2014,7(346):94-94. |
| APA | Zhang, Y.,Qin, WJ.,Qian, ZY.,Liu, XJ.,Wang, H.,...&Tao, J.(2014).Peripheral pain is enhanced by insulin-like growth factor 1 through a G protein-mediated stimulation of T-type calcium channels.SCIENCE SIGNALING,7(346),94-94. |
| MLA | Zhang, Y,et al."Peripheral pain is enhanced by insulin-like growth factor 1 through a G protein-mediated stimulation of T-type calcium channels".SCIENCE SIGNALING 7.346(2014):94-94. |
入库方式： OAI收割
来源：上海神经科学研究所
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