Evidence map›Paper›PMID 20479945›Full record

ArticlePloS one2010

Organophosphorus pesticides decrease M2 muscarinic receptor function in guinea pig airway nerves via indirect mechanisms.

Becky J Proskocil, Donald A Bruun, Charles M Thompson, Allison D Fryer, Pamela J Lein

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

19 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Metformin prevents airway hyperreactivity in rats with dietary obesity.American journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  4. Pioglitazone prevents obesity-related airway hyperreactivity and neuronal MAmerican journal of physiology. Lung cellular and molecular physiology · 2021
    Article
  5. Article
  6. Organophosphorus Pesticides Induce Cytokine Release from Differentiated Human THP1 Cells.American journal of respiratory cell and molecular biology · 2019
    Article
  7. Mechanisms of organophosphorus pesticide toxicity in the context of airway hyperreactivity and asthma.American journal of physiology. Lung cellular and molecular physiology · 2018
    Review
  8. Review
  9. Eosinophil and airway nerve interactions in asthma.Journal of leukocyte biology · 2018
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Environmental exposure to pesticides and respiratory health.European respiratory review : an official journal of the European Respiratory Society · 2015
    Review
  17. Chlorpyrifos exposure and respiratory health among adolescent agricultural workers.International journal of environmental research and public health · 2014
    Article
  18. Article
  19. Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.American journal of physiology. Lung cellular and molecular physiology · 2013
    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 3 institutions in 1 country.

Becky J ProskocilDivision of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
Donald A Bruun
Charles M Thompson
Allison D Fryer
Pamela J Lein
Oregon Health & Science University · USUniversity of California, Davis · USUniversity of Montana · US

Funding

Multidisciplinary Research Training in Pulmonary MedicineT32HL083808 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI LEWINSOHN, DAVID M., SLATORE, CHRISTOPHER G. · 2008 to 2025
$5.3M
Biomarkers of Organophosphate-Adducted ProteinsU01ES016102 · NIEHS · UNIVERSITY OF MONTANA · PI THOMPSON, CHARLES MARK · 2007 to 2010
$2.2M
Role of macrophages in organophosphorus pesticide-induced airway hyperreactivityR01ES017592 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FRYER, ALLISON DEBORAH, LEIN, PAMELA J · 2010 to 2014
$1.7M
Asthma Exacerbation by Organophosphate PesticidesR01ES014601 · NIEHS · OREGON HEALTH & SCIENCE UNIVERSITY · PI FRYER, ALLISON DEBORAH · 2007 to 2011
$1.7M
Organophosphates Modify Eosinophil and Nerve InteractionF32ES014521 · NIEHS · OREGON HEALTH & SCIENCE UNIVERSITY · PI PROSKOCIL, BECKY J · 2006 to 2008
$145k
NHLBI NIH HHS T32 HL083808NIEHS NIH HHS ES014521NIEHS NIH HHS F32 ES014521NIEHS NIH HHS R01 ES014601NIEHS NIH HHS R01-ES014601NIEHS NIH HHS R01 ES017592NIEHS NIH HHS U01 ES016102NIEHS NIH HHS UO1-ES016102
6 · The paper itself

Abstract

backgroundEpidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. METHODOLOGY/PRINCIPAL

findingsIntravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS)-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. CONCLUSIONS/SIGNIFICANCE: These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity.

Indexed as

AnimalsBradycardiaBronchoconstrictionGene Expression RegulationGuinea PigsIleumInjections, IntravenousIn Vitro TechniquesMuscle ContractionMyocardiumNeuronsParaoxonParathionPesticidesPhosphorylationReceptor, Muscarinic M2ParaoxonParathionPesticidesReceptor, Muscarinic M2RNA, Messenger

Identifiers

PMID20479945
PMCPMC2866713
OpenAlexW2138823311

What OpenQuestion holds

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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.