RRC ID 73027
Author Yoshida K, Tanihara S, Miyashita Y, Obayashi K, Ito MA, Yamamoto K, Imai T, Matsuoka I.
Title P2X4 receptor stimulation enhances MrgprB2-mediated mast cell activation and pseudoallergic reactions in mice.
Journal Sci Rep
Abstract Pseudoallergies caused by drugs make disease treatment difficult. Mas-relate G protein-coupled receptor X2 (MRGPRX2), which is specifically expressed in mast cells (MCs), has been implicated in pseudoallergies. High concentrations of therapeutic agents are typically required to stimulate MRGPRX2. Although regulatory mechanisms may enhance this response, the factors involved in this regulation are not well-understood. In this study, the effects of extracellular ATP on MC activation induced by MrgprB2, the mouse ortholog of human MRGPRX2, were examined in mouse peritoneal MCs (PMCs). ATP alone induced minimal PMC degranulation but markedly enhanced degranulation induced by the MrgprB2 agonist compound 48/80 (CP48/80), substance P, PAMP-12, and vancomycin. ATP promoted CP48/80-induced increase in intracellular Ca2+ in PMCs. This enhancement effect of ATP was absent in PMCs prepared from P2X4 receptor (P2X4R)-deficient mice and inhibited by the PI3K inhibitor wortmannin. In addition, P2X4R deficiency reduced the skin-specific and systemic anaphylactic responses to CP48/80 in vivo. In MC-deficient KitW-sh/W-sh mice, reconstitution with MCs obtained from wild-type mice led to a more severe anaphylactic response to CP48/80 compared to that from P2X4R-deficient mice. P2X4R-mediated effect may be involved in MrgprB2-mediated MC activation in vivo and is a potential target for alleviating pseudoallergic reactions.
Volume 12(1)
Pages 18613
Published 2022-11-3
DOI 10.1038/s41598-022-21667-6
PII 10.1038/s41598-022-21667-6
PMID 36329102
PMC PMC9633816
MeSH Adenosine Triphosphate / pharmacology Anaphylaxis* / chemically induced Animals Cell Degranulation* Humans Mast Cells / metabolism Mice Mice, Inbred C57BL Nerve Tissue Proteins / metabolism Phosphatidylinositol 3-Kinases Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Receptors, Neuropeptide / genetics Receptors, Neuropeptide / metabolism Receptors, Purinergic P2X4
IF 3.998
Mice RBRC01888