MAS-related G protein coupled receptor-X2 (MRGPRX2), expressed in human mast cells, is associated with drug-induced pseudo-allergic reactions. Dogs are highly susceptible to drug-induced anaphylactoid reactions caused by various drugs; however, the distribution and physiological function of canine MRGPR family genes, including MRGPRX2, remain largely unknown. In the present study, we clarified the distribution of dog MRGPR family genes by real-time quantitative PCR and in situ hybridisation. We also investigated the stimulatory effects of various histamine-releasing agents, including fluoroquinolones, on HEK293 cells transiently transfected with dog MRGPR family genes to identify their physiological function. Dog MRGPRX2 and MRGPRG were distributed in a limited number of tissues, including the skin (from the eyelid, abdomen, and cheek), whereas MRGPRD and MRGPRF were extensively expressed in almost all tissues examined. Histochemical and in situ hybridisation analyses revealed that MRGPRX2 was expressed in dog connective tissue-type mast cells in the skin. Intracellular Ca²⁺ mobilisation assay revealed that HEK293 cells, expressing dog MRGPRX2 or human MRGPRX2, but not dog MRGPRD, MRGPRF, and MRGPRG, responded to histamine-releasing agents. Our results suggest that dog MRGPRX2 is the functional orthologue of human MRGPRX2 and plays an essential role in drug-induced anaphylactoid reactions in dogs.

MAS 相关 G 蛋白偶联受体-X2 (MRGPRX2) 在人类肥大细胞中表达，与药物引起的假性过敏反应相关。狗对各种药物引起的药物性过敏反应高度敏感；然而，包括MRGPRX2在内的犬MRGPR家族基因的分布和生理功能仍然很大程度上未知。在本研究中，我们通过实时定量PCR和原位杂交阐明了狗MRGPR家族基因的分布。我们还研究了各种组胺释放剂（包括氟喹诺酮类药物）对瞬时转染狗 MRGPR 家族基因的 HEK293 细胞的刺激作用，以鉴定其生理功能。狗MRGPRX2和MRGPRG分布在有限数量的组织中，包括皮肤（眼睑、腹部和脸颊），而MRGPRD和MRGPRF在几乎所有检查的组织中广泛表达。组织化学和原位杂交分析表明，MRGPRX2在狗皮肤结缔组织型肥大细胞中表达。细胞内Ca ²⁺动员测定显示，表达狗MRGPRX2或人MRGPRX2但不表达狗MRGPRD、MRGPRF和MRGPRG的HEK293细胞对组胺释放剂有反应。我们的结果表明，狗 MRGPRX2 是人类 MRGPRX2 的功能直系同源物，并且在狗药物诱导的过敏样反应中发挥重要作用。