Mas-related G protein-coupled receptor D is coupled to endogenous calcium-activated chloride channel in Xenopus oocytes |
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Authors: | Ren-Gong Zhuo Xiao-Yun Ma Pei-Lan Zhou Xiao-Yan Liu Kang Zhang Xiao-Li Wei Hai-Tao Yan Jiang-Ping Xu Jian-Quan Zheng |
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Institution: | 1. Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China 2. Department of Biochemical Pharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China
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Abstract: | 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. |
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