Food allergy (FA) is a common allergic disease without any currently available 
effective drug therapies. Mucosal mast cells (MMCs) play a particularly 
important role in FA, and the increase in their cytosolic Ca(2+) concentration 
([Ca(2+)]cyt) is considered to be a principal component of the degranulation 
process. However, the mechanisms governing Ca(2+) influx remain poorly 
understood in MMCs. Recent reports have highlighted the functions of the 
transient receptor potential melastatin 2 (TRPM2) channel in immunocytes, 
including its role in monocyte chemokine production and macrophage phagocytic 
activity. Although TRPM2 gene expression has been demonstrated in mast cells, 
the significance of such expression remains virtually unknown. In this study, we 
found that antigen-stimulated degranulation was significantly reduced in 
mucosal-type bone marrow-derived mast cells (mBMMCs) prepared from 
TRPM2-knockout (TRPM2-KO) mice (TRPM2-KO mBMMCs) and was suppressed following 
the administration of three TRPM2 inhibitors with different chemical structures, 
including econazole, flufenamic acid (FFA), and 2-aminoethoxydiphenyl borate. 
Furthermore, the antigen-stimulated increase in [Ca(2+)]cyt was significantly 
decreased in TRPM2-KO mBMMCs and was also suppressed by the TRPM2 inhibitors 
econazole and FFA. In addition, thapsigargin-induced increase in [Ca(2+)]cyt was 
significantly decreased in TRPM2-KO mBMMCs. These results suggest that TRPM2 may 
participate in antigen-induced extracellular Ca(2+) influx and subsequent 
degranulation. In addition, TRPM2 inhibitors were shown to improve food allergic 
reactions in a mouse model. Together, these results suggest that TRPM2 
inhibitors suppress MMC degranulation via regulation of the increase in 
[Ca(2+)]cyt. Thus, TRPM2 may play a key role in degranulation by modulating 
intracellular Ca(2+) in MMCs.