PLC-IP3-ORAI pathway participates in the activation of the MRGPRB2 receptor in mouse peritoneal mast cells

•The extracellular calcium ions could promoted activation of MRGPRB2.•PLC-IP3-ORAI was involved in activation of MRGPRB2.•CACCS were involved in MRGPRB2 activation. A novel mast cell-specific G-protein-coupled receptor (GPCR), known as Mas-related G protein-coupled receptor-B2 (MRGPRB2), plays important roles in immune response. However, the opening of ion channels mediated by MRGPRB2 activation remains unclear. In this study, we found that [Ca2+]i elevation and voltage-dependent current generated by MRGPRB2 activation were correlated with extracellular calcium concentration. The increases in [Ca2+]i and voltage-dependent current caused by MRGPRB2 activation were blocked by U73122 (PLC blocker) or 2-APB (IP3 blocker) or synta66 (ORAI blocker). The voltage-dependent current induced by MRGPRB2 was inhibited by calcium-activated chlorine channel (CACCS) blockers, DIDS, or NPPB. Our results indicated the involvement of the PLC-IP3-ORAI signaling pathway and CACCS in MRGPRB2-mediated mast cell activation. [Display omitted]