ACTIONS OF THE INSECTICIDE FIPRONIL, ON DIELDRIN-SENSITIVE AND DIELDRIN-RESISTANT GABA RECEPTORS OF DROSOPHILA-MELANOGASTER

1 Blocking actions of the novel insecticide, fipronil, were examined o n GABA responses recorded from Xenopus oocytes expressing either wild type (dieldrin-sensitive) or mutant (dieldrin-resistant) forms of the Drosphila melanogaster GABA-gated chloride channel homo-oligomer, RDL (the product of the resistance to dieldrin locus: Rdl). 2 In the case of the wild type receptor, fipronil blocked GABA-induced currents indu cing both a shift to the right in the GABA dose-response curve and dep ressing the maximum amplitude of responses to GABA. The potency of fip ronil was dependent on the GABA concentration but was unaffected by me mbrane potential. 3 Mutant RDL GABA-receptors, which have a naturally occurring amino acid substitution (A(302) --> S) in the putative ion-c hannel lining region, conferring resistance to dieldrin and picrotoxin in, were markedly less sensitive to fipronil than the wild-type recept ors. 4 Fipronil antagonism is qualitatively similar to that produced b y the structurally distinct compound, picrotoxinin. As the mutation A( 302) --> S reduces the potency of both fipronil and picrotoxinin, homo oligomeric RDL receptors should facilitate detailed studies of the mol ecular basis of convulsant/insecticide antagonist actions on GABA rece ptors.