title: Actions of insecticides on the insect GABA receptor complex.
abstract: The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 +/- 2.9 nM and a Bmax value of 1770 +/- 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current.
authors.affiliation: School of Biological and Molecular Sciences, Oxford Polytechnic, Headington, Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Bermudez
authors.forename: C A
authors.initials: CA
authors.lastname: Hawkins
authors.forename: A M
authors.initials: AM
authors.lastname: Taylor
authors.forename: D J
authors.initials: DJ
authors.lastname: Beadle
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D006110:Grasshoppers / Q000187:drug effects / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008566:Membranes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010526:Periplaneta / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects*; D013462:Sulfur Radioisotopes
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; C037476:tert-butylbicyclophosphorothionate