| 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
|
| Resource |
| Mice |
RBRC01888 |
