Serotonin Facilitates Peripheral Pain Sensitivity in a Manner That Depends on the Nonproton Ligand Sensing Domain of ASIC3 Channel
文献类型：期刊论文
| 作者 | Wang, X ; Li, WG ; Yu, Y ; Xiao, X ; Cheng, J ; Zeng, WZ ; Peng, Z ; Zhu, MX ; Xu, TL |
| 刊名 | JOURNAL OF NEUROSCIENCE
 |
| 出版日期 | 2013 |
| 卷号 | 33期号:10页码:4265-4279 |
| 关键词 | ROOT GANGLION NEURONS ACID-EVOKED CURRENTS ION CHANNELS SENSORY NEURONS INFLAMMATORY MEDIATORS CAPSAICIN RECEPTOR TISSUE ACIDOSIS VANILLOID RECEPTOR-1 MOLECULAR-CLONING RAT SKIN |
| ISSN号 | 0270-6474 |
| 通讯作者 | Xu, TL (reprint author), Shanghai Jiao Tong Univ, Inst Med Sci, Dept Biochem & Mol Cell Biol, Neurosci Div,Sch Med, 280 South Chongqing Rd, Shanghai 200025, Peoples R China.,xu-happiness@shsmu.edu.cn |
| 英文摘要 | Tissue acidosis and inflammatory mediators play critical roles in inflammatory pain. Extracellular acidosis activates acid-sensing ion channels (ASICs), which have emerged as key sensors for extracellular protons in the central and peripheral nervous systems and play key roles in pain sensation and transmission. Additionally, inflammatory mediators, such as serotonin (5-HT), are known to enhance pain sensation. However, functional interactions among protons, inflammatory mediators, and ASICs in pain sensation are poorly understood. In the present study, we show that 5-HT, a classical pro-inflammatory mediator, specifically enhances the proton-evoked sustained, but not transient, currents mediated by homomeric ASIC3 channels and heteromeric ASIC3/1a and ASIC3/1b channels. Unexpectedly, the effect of 5-HT on ASIC3 channels does not involve activation of 5-HT receptors, but is mediated via a functional interaction between 5-HT and ASIC3 channels. We further show that the effect of 5-HT on ASIC3 channels depends on the newly identified nonproton ligand sensing domain. Finally, coapplication of 5-HT and acid significantly increased pain-related behaviors as assayed by the paw-licking test in mice, which was largely attenuated in ASIC3 knock-out mice, and inhibited by the nonselective ASIC inhibitor amiloride. Together, these data identify ASIC3 channels as an unexpected molecular target for acute actions of 5-HT in inflammatory pain sensation and reveal an important role of ASIC3 channels in regulating inflammatory pain via coincident detection of extracellular protons and inflammatory mediators. |
| 学科主题 | Neurosciences & Neurology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China [31230028, 91132303, 91213306, 31170787]; Key National S&T Program "Major New Drug Development" [2012ZX09504001-003] |
| 语种 | 英语 |
| 公开日期 | 2013-06-04 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/2527]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Wang, X,Li, WG,Yu, Y,et al. Serotonin Facilitates Peripheral Pain Sensitivity in a Manner That Depends on the Nonproton Ligand Sensing Domain of ASIC3 Channel[J]. JOURNAL OF NEUROSCIENCE,2013,33(10):4265-4279. |
| APA | Wang, X.,Li, WG.,Yu, Y.,Xiao, X.,Cheng, J.,...&Xu, TL.(2013).Serotonin Facilitates Peripheral Pain Sensitivity in a Manner That Depends on the Nonproton Ligand Sensing Domain of ASIC3 Channel.JOURNAL OF NEUROSCIENCE,33(10),4265-4279. |
| MLA | Wang, X,et al."Serotonin Facilitates Peripheral Pain Sensitivity in a Manner That Depends on the Nonproton Ligand Sensing Domain of ASIC3 Channel".JOURNAL OF NEUROSCIENCE 33.10(2013):4265-4279. |
入库方式： OAI收割
来源：上海神经科学研究所
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