title: New GABA/glutamate receptor target for [³H]isoxazoline insecticide.
abstract: The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB) binding to house fly head membranes with an IC50 of 0.2 nM in a manner characteristic of GABA-gated chloride channel antagonists. To further define its mode of action, we prepared phenyl-labeled [(3)H]A1443 as described with a specific activity of 14 Ci/mmol. This new radioligand with an apparent IC50 of about 0.4 nM is poorly displaced by most insecticides acting at the [(3)H]EBOB site. Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA/glutamate chloride channel activator site. These findings revive interest in the insect GABA/glutamate receptor as an insecticide target.
authors: Department of Chemistry, University of California, Berkeley , California 94720-1460, United States.
authors: Pablo
authors: P
authors: García-Reynaga
authors: Chunqing
authors: C
authors: Zhao
authors: Richmond
authors: R
authors: Sarpong
authors: John E
authors: JE
authors: Casida
mesh_terms: D000818:Animals; D001665:Binding Sites; D006793:Houseflies; D019476:Insect Proteins / Q000378:metabolism*; D007306:Insecticides / Q000378:metabolism*; D007555:Isoxazoles / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*
chemical_list: C000591860:A1443 compound; D019476:Insect Proteins; D007306:Insecticides; D007555:Isoxazoles; D018079:Receptors, GABA; D017470:Receptors, Glutamate