Dextromethorphan - A widely-used cough suppressant - Induces local anaphylaxis via MRGPRX2 on mast cells

Chem Biol Interact. 2020 Oct 1:330:109248. doi: 10.1016/j.cbi.2020.109248. Epub 2020 Aug 29.

Abstract

Dextromethorphan (DM) is a cough suppressant available in many prescribed and over-the-counter medications. Adverse reactions induced by DM have been regularly reported, including allergic skin reactions in some cases. However, the underlying mechanisms of local anaphylaxis induced by DM have not been elucidated. In this study, we found that DM could activate mast cells to increase calcium mobilization and release β-hexosaminidase, histamine, tumor necrosis factor-α, MCP-1, and IL-8 in a dose-dependent manner. The allergic reactions were confirmed by hind paw swelling and extravasation assay in vivo. Furthermore, DM was revealed to induce local anaphylaxis via MRGPRX2 by the mast cell-deficient kitW-sh/W-sh mice and MRGPRX2 knockdown mast cells. And the MRGPRX2-HEK293/CMC analysis and frontal analysis also showed that DM has a considerable affinity with MRGPRX2. Together, our findings suggest that close monitoring should be drawn on patients with DM for its potential anaphylaxis via MRGPRX2.

Keywords: Allergic reaction; Dextromethorphan; MRGPRX2; Mast cells.

MeSH terms

  • Anaphylaxis / chemically induced*
  • Animals
  • Antitussive Agents / adverse effects
  • Cells, Cultured
  • Dextromethorphan / adverse effects*
  • Dextromethorphan / toxicity
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Neuropeptide / metabolism

Substances

  • Antitussive Agents
  • MRGPRX2 protein, human
  • Mrgprx2 protein, mouse
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Dextromethorphan