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Orthosteric muscarinic receptor activation by the insect repellent IR3535 opens new prospects in insecticide-based vector control

Authors
  • Moreau, Eléonore1
  • Mikulska-Ruminska, Karolina2
  • Goulu, Mathilde1
  • Perrier, Stéphane1
  • Deshayes, Caroline1
  • Stankiewicz, Maria3
  • Apaire-Marchais, Véronique1
  • Nowak, Wieslaw2
  • Lapied, Bruno1
  • 1 Laboratoire Signalisation Fonctionnelle des Canaux Ioniques et des Récepteurs (SiFCIR), UPRES EA 2647, USC INRA 1330, SFR QUASAV 4207, UFR Sciences, Université d’Angers, 2 boulevard Lavoisier, Angers, cedex, 49045, France , Angers (France)
  • 2 Institute of Physics, Faculty of Physics, Astronomy and Informatics, N. Copernicus University, Torun, Poland , Torun (Poland)
  • 3 Faculty of Biological and Veternary Sciences, N. Copernicus University, Torun, Poland , Torun (Poland)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Apr 22, 2020
Volume
10
Issue
1
Identifiers
DOI: 10.1038/s41598-020-63957-x
Source
Springer Nature
License
Green

Abstract

The insect repellent IR3535 is one of the important alternative in the fight against mosquito-borne disease such as malaria, dengue, chikungunya, yellow fever and Zika. Using a multidisciplinary approach, we propose the development of an innovative insecticide-based vector control strategy using an unexplored property of IR3535. We have demonstrated that in insect neurosecretory cells, very low concentration of IR3535 induces intracellular calcium rise through cellular mechanisms involving orthosteric/allosteric sites of the M1-muscarinic receptor subtype, G protein βγ subunits, background potassium channel inhibition generating depolarization, which induces voltage-gated calcium channel activation. The resulting internal calcium concentration elevation increases nicotinic receptor sensitivity to the neonicotinoid insecticide thiacloprid. The synergistic interaction between IR3535 and thiacloprid contributes to significantly increase the efficacy of the treatment while reducing concentrations. In this context, IR3535, used as a synergistic agent, seems to promise a new approach in the optimization of the integrated vector management for vector control.

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