Cross-resistance with dieldrin of a novel tricyclic dinitrile GABA receptor antagonist.
A novel tricyclic dinitrile, KN244, blocked the wild-type (dieldrin-sensitive) homo-oligomeric gamma-aminobutyric acid (GABA)-gated chloride channel of Drosophila melanogaster expressed in Xenopus oocytes. Sensitivity to the block by KN244 of the response to 30 microM GABA (IC50=41.6 nM, wild-type RDLac) was reduced abut 100 fold (IC50=4.5 microM) in the dieldrin-resistant (RDLacA302S) form of RDL.
Matsuda
K
K
The Babraham Institute Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, USA.
Hosie
A M
AM
Holyoke
C W
CW
Rauh
J J
JJ
Sattelle
D B
DB
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004026:Dieldrin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D018756:GABA Antagonists / Q000494:pharmacology*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018079:Receptors, GABA / Q000187:drug effects*; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D018118:Chloride Channels; D018756:GABA Antagonists; D007306:Insecticides; C121752:KN 244; D009570:Nitriles; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D004026:Dieldrin