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Biochemical pharmacology · Dec 2017
MRGPRX2 is essential for sinomenine hydrochloride induced anaphylactoid reactions.
- Rui Liu, Delu Che, Tingting Zhao, Priyanka Pundir, Jiao Cao, Yanni Lv, Jue Wang, Pengyu Ma, Jia Fu, Nana Wang, Xiaoyang Wang, Tao Zhang, Xinzhong Dong, and Langchong He.
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
- Biochem. Pharmacol. 2017 Dec 15; 146: 214-223.
AbstractMast cells are unique immunocytes that function as sentinel cells in host defense reactions such as immediate hypersensitivity responses and anaphylactic responses. The mast cell specific receptor MRGPRX2 (Mas-related G protein-coupled receptor X2) triggers mast cell degranulation-a key process in anaphylactic reactions. We sought to better understand anaphylactic reaction induced by sinomenine hydrochloride (SH). MRGPRX2-related pseudo-allergic reactions induced by SH were investigated using the hindpaw swelling and extravasation assay in vivo and mast cell degranulation assays in vitro. MrgprB2 knockout mice exhibit a reduced SH-induced inflammation effect. Furthermore, MRGPRX2 (the orthologous gene of MrgprB2) related human mast cells are activated by SH in a dose-dependent manner; however, MRGPRX2 knockdown mast cells showed reduced degranulation. The results showed a kind of mechanism that SH-induced anaphylactoid reactions were mediated by MRGPRX2 via activating PLC molecular signaling pathways to provoke mast cells Ca2+ mobilization and degranulation.Copyright © 2017 Elsevier Inc. All rights reserved.
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