Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions
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 M...
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| Veröffentlicht in: | Scientific reports 2020-09, Vol.10 (1), p.16146, Article 16146 |
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| description | 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. |
| doi_str_mv | 10.1038/s41598-020-72819-5 |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-72819-5</identifier><identifier>PMID: 32999394</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/256/2516 ; 631/45/612/194 ; 692/308/153 ; Anaphylactoid reactions ; Anaphylaxis - genetics ; Anaphylaxis - metabolism ; Animals ; Calcium (intracellular) ; Calcium - metabolism ; Calcium mobilization ; Cell Degranulation - drug effects ; Cheek ; Connective tissues ; Dogs ; Dogs - genetics ; Drug Hypersensitivity - genetics ; Drug Hypersensitivity - metabolism ; Eyelid ; Fluoroquinolones ; HEK293 Cells ; Histamine ; Humanities and Social Sciences ; Humans ; Hybridization ; Hypersensitivity ; Mast cells ; Mast Cells - metabolism ; multidisciplinary ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Physiology ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Receptors, Neuropeptide - genetics ; Receptors, Neuropeptide - metabolism ; Science ; Science (multidisciplinary)</subject><ispartof>Scientific reports, 2020-09, Vol.10 (1), p.16146, Article 16146</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c577t-5442a0c42a3064424fb44226b38860e3c25647958f4c8b3bdbf9727a93a015973</citedby><cites>FETCH-LOGICAL-c577t-5442a0c42a3064424fb44226b38860e3c25647958f4c8b3bdbf9727a93a015973</cites><orcidid>0000-0002-0135-2310 ; 0000-0003-1353-264X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527510/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527510/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32999394$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hamamura-Yasuno, Eri</creatorcontrib><creatorcontrib>Iguchi, Takuma</creatorcontrib><creatorcontrib>Kumagai, Kazuyoshi</creatorcontrib><creatorcontrib>Tsuchiya, Yoshimi</creatorcontrib><creatorcontrib>Mori, Kazuhiko</creatorcontrib><title>Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>631/250/256/2516</subject><subject>631/45/612/194</subject><subject>692/308/153</subject><subject>Anaphylactoid reactions</subject><subject>Anaphylaxis - genetics</subject><subject>Anaphylaxis - metabolism</subject><subject>Animals</subject><subject>Calcium (intracellular)</subject><subject>Calcium - metabolism</subject><subject>Calcium mobilization</subject><subject>Cell Degranulation - drug effects</subject><subject>Cheek</subject><subject>Connective tissues</subject><subject>Dogs</subject><subject>Dogs - genetics</subject><subject>Drug Hypersensitivity - genetics</subject><subject>Drug Hypersensitivity - metabolism</subject><subject>Eyelid</subject><subject>Fluoroquinolones</subject><subject>HEK293 Cells</subject><subject>Histamine</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Hypersensitivity</subject><subject>Mast cells</subject><subject>Mast Cells - 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genetics</topic><topic>Anaphylaxis - metabolism</topic><topic>Animals</topic><topic>Calcium (intracellular)</topic><topic>Calcium - metabolism</topic><topic>Calcium mobilization</topic><topic>Cell Degranulation - drug effects</topic><topic>Cheek</topic><topic>Connective tissues</topic><topic>Dogs</topic><topic>Dogs - genetics</topic><topic>Drug Hypersensitivity - genetics</topic><topic>Drug Hypersensitivity - metabolism</topic><topic>Eyelid</topic><topic>Fluoroquinolones</topic><topic>HEK293 Cells</topic><topic>Histamine</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Hypersensitivity</topic><topic>Mast cells</topic><topic>Mast Cells - metabolism</topic><topic>multidisciplinary</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Physiology</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Receptors, Neuropeptide - genetics</topic><topic>Receptors, Neuropeptide - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamamura-Yasuno, Eri</creatorcontrib><creatorcontrib>Iguchi, Takuma</creatorcontrib><creatorcontrib>Kumagai, Kazuyoshi</creatorcontrib><creatorcontrib>Tsuchiya, Yoshimi</creatorcontrib><creatorcontrib>Mori, Kazuhiko</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamamura-Yasuno, Eri</au><au>Iguchi, Takuma</au><au>Kumagai, Kazuyoshi</au><au>Tsuchiya, Yoshimi</au><au>Mori, Kazuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of the dog orthologue of human MAS-related G protein coupled receptor X2 (MRGPRX2) essential for drug-induced pseudo-allergic reactions</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-09-30</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>16146</spage><pages>16146-</pages><artnum>16146</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32999394</pmid><doi>10.1038/s41598-020-72819-5</doi><orcidid>https://orcid.org/0000-0002-0135-2310</orcidid><orcidid>https://orcid.org/0000-0003-1353-264X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/250/256/2516 631/45/612/194 692/308/153 Anaphylactoid reactions Anaphylaxis - genetics Anaphylaxis - metabolism Animals Calcium (intracellular) Calcium - metabolism Calcium mobilization Cell Degranulation - drug effects Cheek Connective tissues Dogs Dogs - genetics Drug Hypersensitivity - genetics Drug Hypersensitivity - metabolism Eyelid Fluoroquinolones HEK293 Cells Histamine Humanities and Social Sciences Humans Hybridization Hypersensitivity Mast cells Mast Cells - metabolism multidisciplinary Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Physiology Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Receptors, Neuropeptide - genetics Receptors, Neuropeptide - metabolism Science Science (multidisciplinary) |
| title | 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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