ArticleScientific reports2022
Determination of key residues in MRGPRX2 to enhance pseudo-allergic reactions induced by fluoroquinolones.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Mutations ofThe journal of allergy and clinical immunology. Global · 2025Review
- The prevalence of genetic variants of the Mas-related G-protein-coupled receptor X2 in patients does not explain perioperative hypersensitivity reactions to neuromuscular blocking agents.Frontiers in pharmacology · 2025Article
- Mast Cells and Mas-related G Protein-coupled Receptor X2: Itching for Novel Pathophysiological Insights to Clinical Relevance.Current allergy and asthma reports · 2024Review
- Non-IgE-Mediated Immediate Drug-Induced Hypersensitivity Reactions.The journal of allergy and clinical immunology. In practice · 2024Article
- Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link.Frontiers in immunology · 2024Review
- Unraveling the venom chemistry with evidence for histamine as key regulator in the envenomation by caterpillarFrontiers in immunology · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MAS-related G protein-coupled receptor X2 (MRGPRX2), expressed in human mast cells, is associated with drug-induced pseudo-allergic reactions. Dogs are highly sensitive to the anaphylactoid reactions induced by certain drugs including fluoroquinolones. Recently, dog MRGPRX2 was identified as a functional ortholog of human MRGPRX2, with dog MRGPRX2 being particularly sensitive to fluoroquinolones. The aim of this study was to determine key residues responsible for the enhanced activity of fluoroquinolone-induced histamine release associated with MRGPRX2. Firstly, a structure model of human and dog MRGPRX2 was built by homology modeling, and docking simulations with fluoroquinolones were conducted. This model indicated that E164 and D184, conserved between human and dog, are essential for the binding to fluoroquinolones. In contrast, F78 (dog: Y) and M109 (dog: W) are unconserved residues, to which the species difference in fluoroquinolone sensitivity is attributable. Intracellular calcium mobilisation assay with human MRGPRX2 mutants, in which residues at positions 78 and 109 were substituted to those of dog MRGPRX2, revealed that M109 and F78 of human MRGPRX2 are crucial residues for enhancing the fluoroquinolone-induced histamine release. In conclusion, these key residues have important clinical implications for revealing the mechanisms and predicting the risks of fluoroquinolone-mediated pseudo-allergic reactions in humans.
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