Evidence map›Paper›PMID 36275683›Full record

ArticleFrontiers in immunology2022

Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist.

Maram Bawazir, Aetas Amponnawarat, Yvonne Hui, Carole A Oskeritzian, Hydar Ali

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

27 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Emerging Therapies for Anaphylaxis.Immunology and allergy clinics of North America · 2026
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  3. MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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  8. Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract.International journal of molecular sciences · 2025
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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 3 countries.

Maram BawazirDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Aetas AmponnawaratDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Yvonne HuiDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, United States.
Carole A OskeritzianDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, United States.
Hydar AliDepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, United States.
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 AR067996NIGMS NIH HHS P20 GM103641
6 · The paper itself

Abstract

Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) contributes to hypersensitivity reactions to cationic US-Food and Drug Administration (FDA) approved drugs such as the neuromuscular blocking agent, rocuronium. In addition, activation of MRGPRX2 by the neuropeptide substance P (SP) and the pro-adrenomedullin peptide (PAMP-12) is associated with a variety of cutaneous conditions such as neurogenic inflammation, pain, atopic dermatitis, urticaria, and itch. Thus, small molecules aimed at blocking MRGPRX2 constitute potential options for modulating IgE-independent MC-mediated disorders. Two inverse MRGPRX2 agonists, named C9 and C9-6, have recently been identified, which inhibit basal G protein activation and agonist-induced calcium mobilization in transfected HEK293 cells. Substance P serves as a balanced agonist for MRGPRX2 whereby it activates both G protein-mediated degranulation and β-arrestin-mediated receptor internalization. The purpose of this study was to determine if C9 blocks MRGPRX2's G protein and β-arrestin-mediated signaling and to determine its specificity. We found that C9, but not its inactive analog C7, inhibited degranulation in RBL-2H3 cells stably expressing MRGPRX2 in response to SP, PAMP-12 and rocuronium with an IC

Indexed as

Drug HypersensitivityNeuropeptidesAdrenomedullinAnaphylatoxinsAnimalsbeta-Arrestinsbeta-N-AcetylhexosaminidasesCalciumCell DegranulationHEK293 CellsHumansImmunoglobulin EMast CellsMiceNerve Tissue ProteinsPertussis ToxinAdrenomedullinAnaphylatoxinsbeta-Arrestinsbeta-N-AcetylhexosaminidasesCalciumImmunoglobulin EMrgprb2 protein, mouseMRGPRX2 protein, humanNerve Tissue ProteinsNeuropeptidesPertussis ToxinReceptors, G-Protein-CoupledReceptors, IgEReceptors, NeuropeptideRocuroniumSubstance Pantagonistmast cell (MC)MRGPRX2MRGPRX2 antagonistPAMP-12rocuroniumsubstance P

Identifiers

PMID36275683
PMCPMC9582160
OpenAlexW4302283182

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Registered trials

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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.