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Molecular Pharmacology Fast Forward
First published on July 18, 2005; DOI: 10.1124/mol.105.015313

0026-895X/05/6804-942-951$20.00
Mol Pharmacol 68:942-951, 2005

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MINIREVIEW

Insect GABA Receptors: Splicing, Editing, and Targeting by Antiparasitics and Insecticides

Steven David Buckingham, Philip Charles Biggin, Benedict Mark Sattelle, Laurence Andrew Brown, and David Barry Sattelle

Medical Research Council Functional Genetics Unit, Department of Human Anatomy and Genetics (S.D.B., B.M.S., L.A.B., D.B.S.) and Department of Biochemistry (P.C.B.), University of Oxford, Oxford, United Kingdom

Ionotropic GABA receptors are abundant in both vertebrate and invertebrate nervous systems, where they mediate rapid, mostly inhibitory synaptic transmission. A GABA-gated chloride channel subunit from Drosophila melanogaster [Resistant to Dieldrin (RDL)] has been cloned, functionally expressed, and found to exhibit many aspects of the pharmacology of native, bicuculline-insensitive insect GABA receptors. RDL is the target of the commercially important insecticide fipronil. A point mutation in the channel-lining region of the RDL molecule is known to underlie most cases of resistance to insecticides acting on GABA receptors. RDL is widely distributed throughout the insect nervous system, but the subunit composition of RDL-containing in native receptors is unknown. It is possible that in some instances, RDL coexpresses with glutamate-gated chloride channel subunits. Other ionotropic receptor subunits (LCCH3 and GRD) form GABA-gated cation channels when heterologously expressed. Interest in RDL as a model ligandgated anion channel has been enhanced by the recent discovery of pre-mRNA A-to-I editing, which, together with alternative splicing, adds to the functional diversity of this GABA receptor subunit.

Received June 2, 2005; accepted July 18, 2005

Address correspondence to: David B. Sattelle, MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK. E-mail: david.sattelle{at}anat.ox.ac.uk




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