Evidence map›Paper›PMID 33467419›Full record

ArticleCells2021

MRGPRX2 Activation by Rocuronium: Insights from Studies with Human Skin Mast Cells and Missense Variants.

Chalatip Chompunud Na Ayudhya, Aetas Amponnawarat, Saptarshi Roy, Carole A Oskeritzian, Hydar Ali

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Mutations ofThe journal of allergy and clinical immunology. Global · 2025
    Review
  6. Article
  7. Non-IgE-Mediated Immediate Drug-Induced Hypersensitivity Reactions.The journal of allergy and clinical immunology. In practice · 2024
    Article
  8. Article
  9. Article
  10. Recent insights into the mechanisms of anaphylaxis.Current opinion in immunology · 2023
    Review
  11. Observational
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. MRGPRX2 and Adverse Drug Reactions.Frontiers in immunology · 2021
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Chalatip Chompunud Na AyudhyaDepartment of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.
Aetas AmponnawaratDepartment of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.
Saptarshi RoyDepartment of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.
Carole A OskeritzianDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 20209, USA.ORCID 0000-0003-1380-9186
Hydar AliDepartment of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104, USA.ORCID 0000-0001-9190-1960
University of Pennsylvania · USUniversity of South Carolina · US

Funding

Targeting early ceramide elevation in pre-symptomatic eczemaP20GM103641 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI ENOS, REILLY, NAGARKATTI, PRAKASH S · 2012 to 2023
$20.7M
Roles of novel MRGPRX2/MrgprB2 signaling in mast cells on host defense and InflammationR01AI149487 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Hydar Ali · 2020 to 2026
$3.9M
Role of a novel human mast cell G protein coupled receptor in Allergy and InflammationR01AI124182 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Hydar Ali · 2016 to 2026
$2.5M
Novel Roles of GRK2 and beta-arrestin2 on mast cell-mediated allergy and InflammationR01AI143185 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ALI, HYDAR · 2020 to 2024
$2.4M
MicroRNAs in atopic dermatitis pathogenesis: a role for mast cell and sphingosine-1-phosphate?R21AR067996 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI OSKERITZIAN, CAROLE A · 2016 to 2017
$323k
NIAID NIH HHS R01 AI124182NIAID NIH HHS R01 AI143185NIAID NIH HHS R01 AI149487NIAMS NIH HHS R21 AR067996
6 · The paper itself

Abstract

Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2's transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor. We found that rocuronium at 20 µg/mL caused degranulation in mouse PMCs via MrgprB2 but required at least 500 µg/mL to induce degranulation in human MCs via MRGPRX2. Furthermore, RBL-2H3 cells transiently expressing M196I, L226P and L237P variants did not display enhanced degranulation in response to rocuronium when compared to the wild-type receptor. These findings provide the first demonstration that rocuronium induces degranulation in human MCs via MRGPRX2. Furthermore, the important differences between MrgprB2 and MRGPRX2 and the inability of rocuronium to induce enhanced response in cells expressing MRGPRX2 variants suggest that the mechanism of its POH is more complex than previously thought.

Indexed as

AnaphylaxisAnimalsCell DegranulationCell LineFemaleHEK293 CellsHumansMaleMast CellsMiceMice, Inbred C57BLMutation, MissenseNerve Tissue ProteinsNeuromuscular Nondepolarizing AgentsProtein DomainsReceptors, G-Protein-CoupledMrgprb2 protein, mouseMRGPRX2 protein, humanNerve Tissue ProteinsNeuromuscular Nondepolarizing AgentsReceptors, G-Protein-CoupledReceptors, NeuropeptideRocuroniumanaphylaxismast cellsmissense mutationMrgprB2MRGPRX2rocuronium

Identifiers

PMID33467419
PMCPMC7830812
OpenAlexW3120490303

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.