Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes

Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes
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Mas 相关 G 蛋白偶联受体 D 与非洲爪蟾卵母细胞内源性钙激活氯离子通道偶联

DOI:
10.1007/s13105-013-0292-1
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发表时间:
2014-03
影响因子:
3.4
通讯作者:
Jian-Quan Zheng
Jian-Quan Zheng
中科院分区:
生物学2区
文献类型:
--
作者:
Xiao-Li Wei;Hai-Tao Yan;Jiang-Ping Xu;Jian-Quan Zheng

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mass相关的G蛋白偶联受体D (MrgD)几乎只表达于痛觉性初级感觉神经元和皮肤颗粒层神经元中。越来越多的证据表明MrgD在疼痛感觉和/或转导中起重要作用。最近的研究表明,该受体也参与了小鼠和人类的瘙痒感觉。在本研究中,我们利用β-丙氨酸(一种假定的MrgD配体)在表达MrgD的爪蟾卵母细胞中发现了一个强大的内向电流。这些电流对Ca2+激活的氯离子通道抑制剂(CaCCs)和细胞内Ca2+螯合剂敏感,表明它们是由内源性CaCCs产生的。此外,研究还表明,在应用磷脂酶C (PLC)抑制剂或肌醇三磷酸受体(IP3R)反义寡核苷酸后,β-丙氨酸诱导的电流显著降低。而蛋白激酶C抑制剂对CaCC电流无明显影响。综上所述,我们的数据表明MrgD的激活通过Gq-PLC-IP3-Ca2+途径促进内源性CaCCs的开放。目前的研究结果揭示了爪蟾卵母细胞中MrgD和CaCCs之间的功能偶联,并提供了一个简单的模型来测定MrgD的活性。
Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively in nociceptive primary sensory neurons and the neurons located in stratum granulosum of skin. More and more evidence suggest that MrgD plays an important role in pain sensation and/or transduction. Recent studies have demonstrated that the receptor is also involved in itch sensation in both mouse and human. In the present study, we identified a robust inward current in MrgD-expressing Xenopus oocytes by using β-alanine, a putative ligand of MrgD. The currents were sensitive to inhibitor of Ca2+-activated chloride channels (CaCCs) and intracellular Ca2+ chelator, suggesting they were produced by endogenous CaCCs. Furthermore, it was demonstrated that upon the application of phospholipase C (PLC) inhibitor, or antisense oligonucleotides of inositol trisphosphate receptor (IP3R), the β-alanine-induced currents were dramatically depressed. However, protein kinase C inhibitor did not display any visible effect on CaCC currents. In summary, our data suggest that the activation of MrgD promotes the open of endogenous CaCCs via Gq-PLC-IP3-Ca2+ pathway. The current findings reveal the functional coupling between MrgD and CaCCs in Xenopus oocytes and also provide a facile model to assay the activity of MrgD.
缓激肽在大鼠感觉神经元中诱导的急性伤害性信号是通过抑制 M 型 K 通道和激活 Ca2 激活的 Cl 通道介导的
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