Publikation:

Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling

Lade...
Vorschaubild

Dateien

Loser_2-1prjxy8weuuks4.pdf
Loser_2-1prjxy8weuuks4.pdfGröße: 2.05 MBDownloads: 168

Datum

2021

Autor:innen

Loser, Dominik
Grillberger, Karin
Hinojosa, Maria G.
Haufe, Yves
Danker, Timm
Johansson, Ylva
Möller, Clemens
Kraushaar, Udo
et al.

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

ArXiv-ID

Internationale Patentnummer

Link zur Lizenz

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Hybrid
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Archives of Toxicology. Springer. 2021, 95(12), pp. 3695-3716. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-021-03168-z

Zusammenfassung

Several neonicotinoids have recently been shown to activate the nicotinic acetylcholine receptor (nAChR) on human neurons. Moreover, imidacloprid (IMI) and other members of this pesticide family form a set of diverse metabolites within crops. Among these, desnitro-imidacloprid (DN-IMI) is of special toxicological interest, as there is evidence (i) for human dietary exposure to this metabolite, (ii) and that DN-IMI is a strong trigger of mammalian nicotinic responses. We set out here to quantify responses of human nAChRs to DN-IMI and an alternative metabolite, IMI-olefin. To evaluate toxicological hazards, these data were then compared to those of IMI and nicotine. Ca2+-imaging experiments on human neurons showed that DN-IMI exhibits an agonistic effect on nAChRs at sub-micromolar concentrations (equipotent with nicotine) while IMI-olefin activated the receptors less potently (in a similar range as IMI). Direct experimental data on the interaction with defined receptor subtypes were obtained by heterologous expression of various human nAChR subtypes in Xenopus laevis oocytes and measurement of the transmembrane currents evoked by exposure to putative ligands. DN-IMI acted on the physiologically important human nAChR subtypes α7, α3β4, and α4β2 (high-sensitivity variant) with similar potency as nicotine. IMI and IMI-olefin were confirmed as nAChR agonists, although with 2-3 orders of magnitude lower potency. Molecular docking studies, using receptor models for the α7 and α4β2 nAChR subtypes supported an activity of DN-IMI similar to that of nicotine. In summary, these data suggest that DN-IMI functionally affects human neurons similar to the well-established neurotoxicant nicotine by triggering α7 and several non-α7 nAChRs.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Live-cell calcium imaging, Pesticide metabolism, Nicotine, Developmental neurotoxicity, Molecular docking, Oocyte recording

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690LOSER, Dominik, Karin GRILLBERGER, Maria G. HINOJOSA, Jonathan BLUM, Yves HAUFE, Timm DANKER, Ylva JOHANSSON, Clemens MÖLLER, Udo KRAUSHAAR, Marcel LEIST, 2021. Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling. In: Archives of Toxicology. Springer. 2021, 95(12), pp. 3695-3716. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-021-03168-z
BibTex
@article{Loser2021-12Acute-55278,
  year={2021},
  doi={10.1007/s00204-021-03168-z},
  title={Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling},
  number={12},
  volume={95},
  issn={0340-5761},
  journal={Archives of Toxicology},
  pages={3695--3716},
  author={Loser, Dominik and Grillberger, Karin and Hinojosa, Maria G. and Blum, Jonathan and Haufe, Yves and Danker, Timm and Johansson, Ylva and Möller, Clemens and Kraushaar, Udo and Leist, Marcel}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/55278">
    <dc:creator>Blum, Jonathan</dc:creator>
    <dc:contributor>Kraushaar, Udo</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/55278/1/Loser_2-1prjxy8weuuks4.pdf"/>
    <dcterms:abstract xml:lang="eng">Several neonicotinoids have recently been shown to activate the nicotinic acetylcholine receptor (nAChR) on human neurons. Moreover, imidacloprid (IMI) and other members of this pesticide family form a set of diverse metabolites within crops. Among these, desnitro-imidacloprid (DN-IMI) is of special toxicological interest, as there is evidence (i) for human dietary exposure to this metabolite, (ii) and that DN-IMI is a strong trigger of mammalian nicotinic responses. We set out here to quantify responses of human nAChRs to DN-IMI and an alternative metabolite, IMI-olefin. To evaluate toxicological hazards, these data were then compared to those of IMI and nicotine. Ca2+-imaging experiments on human neurons showed that DN-IMI exhibits an agonistic effect on nAChRs at sub-micromolar concentrations (equipotent with nicotine) while IMI-olefin activated the receptors less potently (in a similar range as IMI). Direct experimental data on the interaction with defined receptor subtypes were obtained by heterologous expression of various human nAChR subtypes in Xenopus laevis oocytes and measurement of the transmembrane currents evoked by exposure to putative ligands. DN-IMI acted on the physiologically important human nAChR subtypes α7, α3β4, and α4β2 (high-sensitivity variant) with similar potency as nicotine. IMI and IMI-olefin were confirmed as nAChR agonists, although with 2-3 orders of magnitude lower potency. Molecular docking studies, using receptor models for the α7 and α4β2 nAChR subtypes supported an activity of DN-IMI similar to that of nicotine. In summary, these data suggest that DN-IMI functionally affects human neurons similar to the well-established neurotoxicant nicotine by triggering α7 and several non-α7 nAChRs.</dcterms:abstract>
    <dcterms:issued>2021-12</dcterms:issued>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/55278"/>
    <dcterms:title>Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling</dcterms:title>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Loser, Dominik</dc:creator>
    <dc:contributor>Haufe, Yves</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-10-18T15:01:17Z</dc:date>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/55278/1/Loser_2-1prjxy8weuuks4.pdf"/>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:contributor>Hinojosa, Maria G.</dc:contributor>
    <dc:contributor>Danker, Timm</dc:contributor>
    <dc:creator>Grillberger, Karin</dc:creator>
    <dc:creator>Leist, Marcel</dc:creator>
    <dc:creator>Hinojosa, Maria G.</dc:creator>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-10-18T15:01:17Z</dcterms:available>
    <dc:creator>Johansson, Ylva</dc:creator>
    <dc:contributor>Blum, Jonathan</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:contributor>Grillberger, Karin</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Loser, Dominik</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Kraushaar, Udo</dc:creator>
    <dc:creator>Haufe, Yves</dc:creator>
    <dc:contributor>Johansson, Ylva</dc:contributor>
    <dc:contributor>Möller, Clemens</dc:contributor>
    <dc:creator>Danker, Timm</dc:creator>
    <dc:language>eng</dc:language>
    <dc:creator>Möller, Clemens</dc:creator>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt
URL der Originalveröffentl.

Prüfdatum der URL

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen