title: Blocking actions of BIDN, a bicyclic dinitrile convulsant compound, on wild-type and dieldrin-resistant GABA receptor homo-oligomers of Drosophila melanogaster expressed in Xenopus oocytes.
abstract: The receptor antagonist actions are described for a novel bicyclic dinitrile compound (BIDN, 3,3-bis-(trifluoromethyl)-bicyclo [2.2.1] heptane-2,2-dicarbonitrile) on a Drosophila melanogaster homo-oligomeric GABA receptor expressed in Xenopus oocytes. BIDN blocked the wild-type form of the receptor in a neither purely competitive, nor purely non-competitive manner, being dependent on the GABA concentration yet insurmountable, and block was independent of the membrane potential. BIDN was found to be less effective against a mutant (A(302) --> S) form of the receptor resistant to dieldrin and picrotoxinin. This cross resistance of dieldrin-resistant receptors to BIDN is of interest in the light of recent findings that BIDN binding to insect membranes is displaced competitively by dieldrin, but not by picrotoxinin.
authors.affiliation: Babraham Institute Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Hosie
authors.forename: Y
authors.initials: Y
authors.lastname: Shirai
authors.forename: S D
authors.initials: SD
authors.lastname: Buckingham
authors.forename: J J
authors.initials: JJ
authors.lastname: Rauh
authors.forename: R T
authors.initials: RT
authors.lastname: Roush
authors.forename: H A
authors.initials: HA
authors.lastname: Baylis
authors.forename: D B
authors.initials: DB
authors.lastname: Sattelle
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D003292:Convulsants / Q000494:pharmacology*; D004026:Dieldrin / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000737:chemistry*; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000502:physiology; D008845:Microinjections; D009570:Nitriles / Q000494:pharmacology*; D009842:Oligopeptides; D009865:Oocytes / Q000502:physiology; D018079:Receptors, GABA / Q000235:genetics / Q000648:ultrastructure; D014981:Xenopus; D005466:Fluorocarbons
chemical_list: D001643:Bridged Bicyclo Compounds; D018118:Chloride Channels; D003292:Convulsants; D004026:Dieldrin; D018756:GABA Antagonists; D009570:Nitriles; D009842:Oligopeptides; D018079:Receptors, GABA; C098123:3,3-bis(trifluoromethyl)bicyclo(2.2.1)heptane-2,2-dicarbonitrile; D005466:Fluorocarbons