摘要
目的
研究阿片受体与神经递质转运蛋白和钠钾泵在针刺镇痛中的可能机制。
方法
利用爪蟾卵母细胞所建立的异源性蛋白表达模型, 通过基因显微注射技术, 应用双电极电压钳方法检测所表达靶蛋白的跨膜稳态电流。
结果
δ-阿片受体 (DOR) 与γ-氨基丁酸转运蛋白 (GAT1) 、 谷氨酸转运蛋白 (EAAC1) 或钠钾泵共表达均可降低神经递质转运蛋白的活性, 阿片受体的激活以不同方式影响转运蛋白的活性: 1) GAT1 活性被进一步抑制; 2) EAAC1 活性增强; 3) 钠钾泵被抑制会导致DOR对激动剂 (DPDPE) 的敏感性增加。
结论
DOR的激活可使突触间隙的GABA水平增加, 而谷氨酸浓度减少, 钠钾泵的抑制导致阿片受体激动剂的敏感性增加, 我们认为内源性哇巴因可能放大了这些效应。 这些协同性效应可能是痛觉抑制和/或针刺镇痛的分子机制。
Abstract
Objective
To investigate the possible mechanisms in acupuncture analgesia by interaction of δ-opioid receptor with neurotransmitter transport proteins or the Na+-K+ pump.
Methods
Microinjection of respective heterologous cRNA into the Xenopus oocytes as a model system, and measurement of steady-state currents under two-electrode voltage clamp.
Results
The co-expression of the δ-opioid receptor with GAT1, EAAC1 or the sodium pump resulted in reducing activity of the respective transporter. Opioid receptor activation affected transporter activity in different ways: 1) GAT1 was further inhibited; 2) EAAC1 was stimulated; 3) Na+-K+ pump activity interfered with agonist sensitivity of DOR. Pump inhibition led to higher sensitivity for DPDPE.
Conclusion
GABA transporter inhibition and glutamate transporter stimulation may counteract pain sensation by affecting the neurotransmitter concentration in the synaptic cleft and, therefore, may contribute synergistically to pain suppression by acupuncture. Sodium pump inhibition by endogenous ouabain may amplify these effects. These synergistic effects may be the molecular mechanism of inhibiting pain sense and/or acupuncture analgesia.
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References
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HU JH, YANG N, MA YH, et al. Hyperalgesic Effects of γ-Aminobutyric Acid Transporter I in Mice. J Neurosci Res. 2003, 73(4): 565–572.
XIA P, PEI G, SCHWARZ W. Regulation of the Glutamate Transporter EAAC1 by Expression and Activation of δ-opioid Receptor. Eur J Neurosci, 2006, 24(1): 87–93.
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Authors and Affiliations
Additional information
Fund Items: the Science Foundation of Shanghai Municipal Commission of Science and Technology (05DZ19745, 06DZ19732, 064319053, 07DZ19722, 07DZ19733), the National Basic Research Program of China (973 Program, 2005CB523306) and Shanghai Leading Academic Discipline Project (B112 and T0302)
Author: YANG Zhi-jie, 42 years old, associate researcher, research Interest are cellular mechanisms of acupuncture analgesia and moxibustion
Research Interest: cellular electrophysiology inacupuncture and Chinese Medicine research
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Yang, ZJ., Bao, GB., Deng, HP. et al. Interaction of δ-opioid receptor with membrane transporters: Possible mechanisms in pain suppression by acupuncture. J. Acupunct. Tuina. Sci. 6, 298–300 (2008). https://doi.org/10.1007/s11726-008-0298-3
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DOI: https://doi.org/10.1007/s11726-008-0298-3
关键词
Key Words
- Acupuncture Analgesia
- Receptors, Opioid
- Neurotransmitter Transport Proteins
- Protein Interaction Domains and Motifs