Evidence map›Paper›PMID 25517090›Full record

ArticleNature2015

Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions.

Benjamin D McNeil, Priyanka Pundir, Sonya Meeker, Liang Han, Bradley J Undem, Marianna Kulka, Xinzhong Dong

Registry-linked trialAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03157180 (The Clinical Study on Pseudo-allergic Reaction to Anesthetic Drugs During General Anesthesia), which is not on this map. Cited by 541 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
541citing papers in PubMed, 1 pooled it
22.5field-weighted citation impact, top 1% 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.

NCT03157180 unknown statusnot on this mapstarted 2017, after this paper: background citation

The Clinical Study on Pseudo-allergic Reaction to Anesthetic Drugs During General Anesthesia

Typeobservational_patient_registrySponsorCentral South UniversityRan2017 to 2019Enrolled200ConditionsGeneral Anesthetic Drug Allergy
3 · Its place in the literature

Who cites it

541 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,245 citations in OpenAlex.

  1. Guideline
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  17. Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Review
  18. Review
  19. An Itch Receptor Drives Melanoma.bioRxiv : the preprint server for biology · 2026
    Article
  20. Article

481 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Benjamin D McNeilThe Solomon H. Snyder Department of Neuroscience, Department of Neurosurgery, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Priyanka PundirDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Sonya MeekerDepartment of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Liang HanThe Solomon H. Snyder Department of Neuroscience, Department of Neurosurgery, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Bradley J UndemDepartment of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Marianna Kulka1] Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2E1, Canada [2] National Institute for Nanotechnology, National Research Council Canada, Edmonton, Alberta T6G 2M9, Canada.
Xinzhong Dong1] The Solomon H. Snyder Department of Neuroscience, Department of Neurosurgery, Center for Sensory Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA [2] Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Johns Hopkins University · USUniversity of Alberta · CA

Funding

Functional analysis of the Mrg receptor family in pain sensationR01NS054791 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DONG, XINZHONG · 2007 to 2020
$5.0M
Functional Analysis of Pirt and Pirt2: novel regulators of TRP channelsR01GM087369 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI DONG, XINZHONG · 2010 to 2013
$1.3M
Molecular and Cellular Mechanisms of Itch SensationK99NS087088 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HAN, LIANG · 2014 to 2015
$190k
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM087369NIGMS NIH HHS R01GM087369NINDS NIH HHS K99 NS087088NINDS NIH HHS R01 NS054791NINDS NIH HHS R01NS054791
6 · The paper itself

Abstract

Mast cells are primary effectors in allergic reactions, and may have important roles in disease by secreting histamine and various inflammatory and immunomodulatory substances. Although they are classically activated by immunoglobulin (Ig)E antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions. The pathogenic roles of these substances have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, Mrgprb2, the orthologue of the human G-protein-coupled receptor MRGPRX2. Secretagogue-induced histamine release, inflammation and airway contraction are abolished in Mrgprb2-null mutant mice. Furthermore, we show that most classes of US Food and Drug Administration (FDA)-approved peptidergic drugs associated with allergic-type injection-site reactions also activate Mrgprb2 and MRGPRX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that Mrgprb2 and MRGPRX2 are targets of many small-molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice; and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MRGPRX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.

Indexed as

AnimalsDisease Models, AnimalDrug HypersensitivityFemaleHEK293 CellsHistamine ReleaseHumansInflammationMaleMast CellsMiceMice, KnockoutNerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, NeuropeptideMrgprb2 protein, mouseMRGPRX2 protein, humanNerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, Neuropeptide

Identifiers

PMID25517090
PMCPMC4359082
OpenAlexW2056811697

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.