Orthosteric muscarinic receptor activation by the insect repellent IR3535 opens new prospects in insecticide-based vector control.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
21
11
2019
accepted:
08
04
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
25
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32321987
doi: 10.1038/s41598-020-63957-x
pii: 10.1038/s41598-020-63957-x
pmc: PMC7176678
doi:
Substances chimiques
Insect Proteins
0
Insecticides
0
Receptors, Muscarinic
0
beta-Alanine
11P2JDE17B
insect repellent M 3535
95328-09-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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