title: Afidopyropen: New and potent modulator of insect transient receptor potential channels.
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.
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Ramani
authors.initials: R
authors.lastname: Kandasamy
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Damian
authors.initials: D
authors.lastname: London
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Stam
authors.affiliation: BASF SE, Carl-Bosch-Str. 38, Ludwigshafen 67056, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: von Deyn
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Xilong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Salgado
authors.affiliation: BASF Corporation, 26 Davis Drive, Research Triangle Park, NC 27709, USA. Electronic address: alexandre.nesterov@basf.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Nesterov
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D006110:Grasshoppers / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000633:toxicity*; D019476:Insect Proteins / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D007783:Lactones / Q000633:toxicity*; D009536:Niacinamide / Q000031:analogs & derivatives; D050051:Transient Receptor Potential Channels / Q000187:drug effects*; D014227:Triazines
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D019476:Insect Proteins; D007306:Insecticides; D007783:Lactones; D050051:Transient Receptor Potential Channels; D014227:Triazines; C000622232:afidopyropen; D009536:Niacinamide; C524822:flonicamid; C480311:pymetrozine
keywords: Afidopyropen; Flonicamid; Insecticides; Pymetrozine; Receptor binding; TRPV channels