Activation of MRGPRB2 receptor in mouse peritoneal mast cells depends on PLC-IP3-ORAI1 pathway

OBJECTIVE A novel mast cell-specific G-protein-coupled receptor(GPCR),known as mas-related GPCR-B2(MRGPRB2),plays important roles in the immune response.The opening of ion channels mediated by MRGPRB2 activation remains unclear.METHODS AND RE⁃SULTS Calcium influx induced by activation of MRGPRB2 receptor in mouse peritoneal mast cells was related to the concentrations of calcium ions in the extracellular solution.Similarly,the volt⁃age-dependent current generated by MRGPRB2 activation was also correlated with the extracellu⁃lar calcium concentration.In addition,the in⁃creased of calcium influx or voltage-dependent current caused by activation of MrgprB2 could be blocked by U73122(PLC blocker)or 2-APB(IP3-ORAI1 blocker).Meanwhile,calcium-activated chlorine channel(TMEM16A)was involved in the generation of voltage-dependent currents in⁃duced by MRGPRB2 activation in mouse perito⁃neal mast cells.Furthermore,the degranulation of mouse peritoneal mast cells mediated by MRGPRB2 receptor could also be inhibited by U73122 or 2-APB.CONCLUSION PLC-IP3-ORAI1-TMEM16A signaling pathway was involved in MRGPRB2-mediated mast cell activation.

肥大细胞激活相关受体及其功能研究进展

肥大细胞广泛分布于机体各个部位,常见于机体与外部环境之间的粘膜表面,是重要的免疫细胞之一,在固有免疫、适应性免疫及免疫调节中发挥着重要的作用。研究表明,肥大细胞的过度激活与哮喘、过敏性鼻炎、食物过敏、急慢性瘙痒等过敏性及炎性疾病的发生、发展密切相关,主要表现为肥大细胞向炎症部位浸润并释放多种过敏介质。阻断肥大细胞激活可作为有效治疗过敏性及炎性疾病的手段之一,因此与肥大细胞激活相关的受体是临床药物开发的有效靶点。激活肥大细胞的相关受体种类较多,并且不同的受体所介导产生的效应也不尽相同,新的肥大细胞受体不断被发现,然而,对这些研究的梳理比较少。本综述总结了参与肥大细胞激活的相关受体,依据不同效应对受体进行分类,并对其下游信号通路及应用进行阐述。