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  • Title: Cisatracurium induces mast cell activation and pseudo-allergic reactions via MRGPRX2.
    Author: Che D, Rui L, Cao J, Wang J, Zhang Y, Ding Y, Zhao T, Ma P, An H, Gao Z, Zhang T.
    Journal: Int Immunopharmacol; 2018 Sep; 62():244-250. PubMed ID: 30032049.
    Abstract:
    BACKGROUND: Pseudo-allergic reactions occur when patients receive muscle relaxants during perioperative anesthesia. These reactions may result in a serious threat to the patient's life, particularly to a child's life. Cisatracurium, a relatively new NMBA, has resulted in bronchospasms and cardiovascular collapse. However, the mechanisms underlying the anaphylactoid reactions caused by cisatracurium have not been fully elucidated. METHODS: In the present study, the MRGPRX2-related pseudo-allergic reactions induced by cisatracurium were investigated using hindpaw swelling and extravasation assays in vivo and mast cell degranulation assays. RESULTS: Cisatracurium caused anaphylactoid reactions in wild-type mice. However, cisatracurium did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, mast cell-related G protein-coupled receptor B2-knockout mice did not display an inflammatory response upon treatment with cisatracurium. Cisatracurium induced LAD2 cell degranulation, leading to the dose-dependent release of β-hexosaminidase, histamine and TNF-α. However, cisatracurium only induced the release of low levels of these mediator LAD2 cells transfected with MRGPRX2 siRNA. Cisatracurium also stimulated intracellular Ca2+ influx in MRGPRX2-HEK293 cells compared with that in NC-HKE293 cells. Interestingly, cytokine release was not observed in LAD2 cells even with high dose of cisatracurium. CONCLUSIONS: Cisatracurium activated MRGPRX2 and triggered mast cell degranulation, leading to anaphylactoid reactions. Therefore, strategies targeting MRGPRX2 might potentially block cisatracurium-induced pseudo-allergic reactions.
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