House fly brain γ-aminobutyric acid-gated chloride channel: target for multiple classes of insecticides

Abstract

The γ-aminobutyric acid receptor/chloride ionophore is the proposed target in insects for a wide range of commercial and candidate insecticides, a hypothesis that can be tested directly by developing a toxicologically relevant radioligand binding assay. This was achieved with house fly brain and 1-(4-ethynylphenyl)-4-[2,3- 3H 2]propyl-2,6,7-trioxabicyclo[2.2.2]octane ([ 3H]EBOB) for which the binding site was demonstrated to be identical to or overlapping with that of seven classes of structurally diverse insecticides, i.e., trioxabicyclooctanes, dithianes, silatranes, lindane, toxaphene, chlorinated cyclodienes, and picrotoxinin. The affinity of the binding site for this radioligand is reduced fourfold in a cyclodiene-resistant strain. There is no cross resistance to avermectin B 1a and moxidectin which are potent noncompetitive inhibitors of [ 3H]EBOB binding.