Afidopyropen: New and potent modulator of insect transient receptor potential channels. (May 2017)

• Record Type: Journal Article
• Authors: Kandasamy, Ramani; London, Damian; Stam, Lynn; von Deyn, Wolfgang; Zhao, Xilong; Salgado, Vincent L.; Nesterov, Alexandre
• Is Part Of: Insect biochemistry and molecular biology. Volume 84(2017)
• Page Start: 32
• Page End: 39
• Publication Date: 2017-05
• Subjects: Afidopyropen -- Pymetrozine -- Flonicamid -- TRPV channels -- Receptor binding -- Insecticides; AP afidopyropen -- PM pymetrozine -- FL flonicamid -- TFNA-AM 4-trifluoronicotinamide; Insect biochemistry -- Periodicals; Insects -- Physiology -- Periodicals; Insects -- Molecular aspects -- Periodicals; Biochemistry -- Periodicals; Insectes -- Biochimie -- Périodiques; Insectes -- Composition -- Périodiques; Insectes -- Physiologie -- Périodiques; Insectes -- Aspect moléculaire -- Périodiques; Biochimie -- Périodiques; Biochemistry; Insect biochemistry; Insects -- Molecular aspects; Insects -- Physiology; Periodicals; 572.8157
• DOI: 10.1016/j.ibmb.2017.03.005
• Languages: English
• ISSNs: 0965-1748

Abstract

Abstract: The commercial insecticides pymetrozine and pyrifluquinazon control plant-sucking pests by disturbing their coordination and ability to feed. We have previously shown that these compounds act by overstimulating and eventually silencing vanilloid-type transient receptor potential (TRPV) channels, which consist of two proteins, Nanchung and Inactive, that are co-expressed exclusively in insect chordotonal stretch receptor neurons. Here we show that a new insecticidal compound, afidopyropen, modulates chordotonal organs of American grasshoppers ( Schistocerca americana ) in the same fashion. Afidopyropen stimulated heterologously expressed TRPV channels from two different insect species - fruit fly ( Drosophila melanogaster ) and pea aphid ( Acyrthosiphon pisum ) - but did not affect function of the mammalian TRPV channel TRPV4. Activation of the insect TRPVs required simultaneous expression of both Nanchung and Inactive proteins. Tritium-labeled afidopyropen bound fruit fly TRPVs with higher affinity than pymetrozine and competed with pymetrozine for binding. Nanchung protein formed the main binding interface for afidopyropen, whereas co-expression of Inactive dramatically increased binding affinity. Another modulator of chordotonal organs, flonicamid, did not activate insect TRPV channels, nor did it compete with afidopyropen for binding, indicating that it has a different target site. These results define afidopyropen as a new, potent and specific modulator of insect TRPV channels, and provide insight into the unique binding mode of these compounds. Graphical abstract: Highlights: A new insecticide, afidopyropen, acts modulating insect TRPV channels - heteromers of Nanchung and Inactive proteins. Afidopyropen is more potent than pymetrozine against TRPV channels from two insect species in an in vitro functional assay. Afidopyropen and pymetrozine have overlapping binding sites, with afidopyropen having higher affinity than pymetrozine. Nanchung forms the main binding interface, whereas Inactive dramatically increases binding affinities of both insecticides. Another modulator of chordotonal organs, flonicamid, acts at different target site than afidopyropen and pymetrozine.