{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:16:22Z","timestamp":1772691382306,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,20]],"date-time":"2020-12-20T00:00:00Z","timestamp":1608422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001136","name":"Australian and New Zealand College of Anaesthetists","doi-asserted-by":"publisher","award":["18\u2010039"],"award-info":[{"award-number":["18\u2010039"]}],"id":[{"id":"10.13039\/501100001136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neuromuscular\u2010blocking agents (NMBAs) can cause both IgE\u2010dependent and IgE\u2010independent anaphylactic reactions, with activation of the mast cell receptor MRGPRX2 being important to the latter. Sugammadex, a reversal agent for certain aminosteroid NMBAs, has been proposed as an antidote for these anaphylactic events with conflicting outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We further characterize the involvement of MRGPRX2 in NMBA\u2010induced mast cell activation and determine how this is influenced by sugammadex. We then apply these <jats:italic>in vitro<\/jats:italic> results to infer the possible utility of sugammadex in the acute management of non\u2010IgE\u2010dependent anaphylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The LAD2 human mast cell line and a MRGPRX2 knock\u2010down derivative were used to validate the involvement of MRGPRX2 and to test the effect of sugammadex on mast cell activation by NMBAs and other MRGPRX2 agonists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All MRGPRX2 agonists tested were shown to induce MRGPRX2\u2010dependent LAD2 mast cell calcium mobilization and cytokine release and all, apart from rocuronium, induced degranulation. Co\u2010treatment of mast cells with sugammadex and some MRGPRX2 agonists significantly reduced cell activation, but if sugammadex was administered a few minutes following stimulation, degranulation was not attenuated. However, addition of sugammadex up to 180\u00a0min following LAD2 MRGPRX2 stimulation, significantly reduced CCL2 mRNA and protein induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>We show that sugammadex, known to reverse muscle blockade by certain NMBAs, is also able to reduce MRGPRX2 activation by NMBAs and other, but not all, MRGPRX2 agonists. As sugammadex was ineffective in attenuating mast cell degranulation when added rapidly post MRGPRX2 activation, this suggests against the agent having efficacy in controlling acute symptoms of anaphylaxis to NMBAs caused by MRGPRX2 activation. Interestingly, however, sugammadex did impair MRGPRX2\u2010induced CCL2 release, suggesting that it may have some benefit in perhaps dampening less well\u2010defined adverse effects of MRGPRX2\u2010dependent anaphylaxis associated with the more slowly elaborated mast cell mediators.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13801","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T20:03:18Z","timestamp":1607112198000},"page":"685-695","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["MRGPRX2 activation in mast cells by neuromuscular blocking agents and other agonists: Modulation by sugammadex"],"prefix":"10.1111","volume":"51","author":[{"given":"Nithya A.","family":"Fernandopulle","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics The University of Melbourne Parkville Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie S.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics The University of Melbourne Parkville Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul F.","family":"Soeding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics The University of Melbourne Parkville Vic. Australia"},{"name":"Department of Anaesthetics and Pain Medicine The Royal Melbourne Hospital Parkville Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-1304","authenticated-orcid":false,"given":"Graham A.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics The University of Melbourne Parkville Vic. 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