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Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
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Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
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Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
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Journal Article
Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
2020
Overview
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 Ca
2+
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Cell Degranulation - drug effects
/ Cheek
/ Dogs
/ Drug Hypersensitivity - genetics
/ Drug Hypersensitivity - metabolism
/ Eyelid
/ Humanities and Social Sciences
/ Humans
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Receptors, Neuropeptide - genetics
/ Receptors, Neuropeptide - metabolism
/ Science
