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. 1995 Jul;115(6):909–912. doi: 10.1111/j.1476-5381.1995.tb15896.x

Actions of the insecticide fipronil, on dieldrin-sensitive and- resistant GABA receptors of Drosophila melanogaster.

A M Hosie 1, H A Baylis 1, S D Buckingham 1, D B Sattelle 1
PMCID: PMC1909003  PMID: 7582519

Abstract

1. Blocking actions of the novel insecticide, fipronil, were examined on GABA responses recorded from Xenopus oocytes expressing either wild type (dieldrin-sensitive) or mutant (dieldrin-resistant) forms of the Drosophila 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 inducing both a shift to the right in the GABA dose-response curve and depressing the maximum amplitude of responses to GABA. The potency of fipronil was dependent on the GABA concentration but was unaffected by membrane potential. 3. Mutant RDL GABA-receptors, which have a naturally occurring amino acid substitution (A302-->S) in the putative ion-channel lining region, conferring resistance to dieldrin and picrotoxinin, were markedly less sensitive to fipronil than the wild-type receptors. 4. Fipronil antagonism is qualitatively similar to that produced by the structurally distinct compound, picrotoxinin. As the mutation A302-->S reduces the potency of both fipronil and picrotoxinin, homooligomeric RDL receptors should facilitate detailed studies of the molecular basis of convulsant/insecticide antagonist actions on GABA receptors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anthony N. M., Harrison J. B., Sattelle D. B. GABA receptor molecules of insects. EXS. 1993;63:172–209. doi: 10.1007/978-3-0348-7265-2_8. [DOI] [PubMed] [Google Scholar]
  2. Buckingham S. D., Hosie A. M., Roush R. L., Sattelle D. B. Actions of agonists and convulsant antagonists on a Drosophila melanogaster GABA receptor (Rdl) homo-oligomer expressed in Xenopus oocytes. Neurosci Lett. 1994 Nov 7;181(1-2):137–140. doi: 10.1016/0304-3940(94)90578-9. [DOI] [PubMed] [Google Scholar]
  3. Cole L. M., Roush R. T., Casida J. E. Drosophila GABA-gated chloride channel: modified [3H]EBOB binding site associated with Ala-->Ser or Gly mutants of Rdl subunit. Life Sci. 1995;56(10):757–765. doi: 10.1016/0024-3205(95)00006-r. [DOI] [PubMed] [Google Scholar]
  4. Ffrench-Constant R. H., Mortlock D. P., Shaffer C. D., MacIntyre R. J., Roush R. T. Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor locus. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7209–7213. doi: 10.1073/pnas.88.16.7209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ffrench-Constant R. H., Rocheleau T. A., Steichen J. C., Chalmers A. E. A point mutation in a Drosophila GABA receptor confers insecticide resistance. Nature. 1993 Jun 3;363(6428):449–451. doi: 10.1038/363449a0. [DOI] [PubMed] [Google Scholar]
  6. Millar N. S., Buckingham S. D., Sattelle D. B. Stable expression of a functional homo-oligomeric Drosophila GABA receptor in a Drosophila cell line. Proc Biol Sci. 1994 Dec 22;258(1353):307–314. doi: 10.1098/rspb.1994.0178. [DOI] [PubMed] [Google Scholar]
  7. Newland C. F., Cull-Candy S. G. On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat. J Physiol. 1992 Feb;447:191–213. doi: 10.1113/jphysiol.1992.sp018998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Thompson M., Steichen J. C., ffrench-Constant R. H. Conservation of cyclodiene insecticide resistance-associated mutations in insects. Insect Mol Biol. 1993;2(3):149–154. doi: 10.1111/j.1365-2583.1993.tb00134.x. [DOI] [PubMed] [Google Scholar]
  9. Zhang H. G., ffrench-Constant R. H., Jackson M. B. A unique amino acid of the Drosophila GABA receptor with influence on drug sensitivity by two mechanisms. J Physiol. 1994 Aug 15;479(Pt 1):65–75. doi: 10.1113/jphysiol.1994.sp020278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. ffrench-Constant R. H., Steichen J. C., Rocheleau T. A., Aronstein K., Roush R. T. A single-amino acid substitution in a gamma-aminobutyric acid subtype A receptor locus is associated with cyclodiene insecticide resistance in Drosophila populations. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1957–1961. doi: 10.1073/pnas.90.5.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]

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