INSECTICIDE BINDING-SITES ON GAMMA-AMINOBUTYRIC-ACID RECEPTORS OF INSECTS AND MAMMALS

The gamma-aminobutyric acid (GABA) receptor of insects and mammals has two binding sites or domains that are sensitive to nanomolar levels of selected highly effective insecticides. One of these is the noncompetitive blocker (NCB) site where the polychlorocycloalkanes (PCCAs), picrotoxinin (PTX), 2,6,7-trioxabicyclo[2.2.2]octanes (TBOs), and dithianes act to block the integral chloride channel of the GABA receptor complex. The other site interacts with insecticidal GABA-gated chloride channel activators exemplified by avermectin B1a. (AVM). Binding studies with [H-3]TBOs, [H-3]AVM, and radioligands specific for other sites on the receptor complex as well as chloride flux measurements serve to define the properties of the binding sites, the coupling between the NCB, AVM, and other sites, the nature of target site alterations in resistant strains, and the contribution of species-dependent receptor diversity to selective toxicity.