title: gamma-Aminobutyric acid receptor ionophore complexes: differential effects of deltamethrin, dichlorodiphenyltrichloroethane, and some novel insecticides in a rat brain membrane preparation.
abstract: The binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS), a gamma-aminobutyric acid (GABA)-activated chloride ionophore ligand; [3H]diazepam, a benzodiazepine agonist; and [3H]muscimol, a GABA receptor probe, were used to assess the effects at 100 microM of deltamethrin, dichlorodiphenyltrichloroethane (DDT), and three experimental insecticides--a DDT-pyrethroid hybrid, GH414 (cycloprothrin), and two DDT-analogues, GH266 and GH149 (EDO), on GABA receptor ionophore complexes in a rat brain membrane preparation. GH266 and GH149 were found to inhibit a greater percentage of [35S]TBPS binding than the same concentration of deltamethrin or DDT, although GH414 had little effect. GH266 and GH149 enhanced [3H]diazepam binding by nearly 200%, in contrast to the inhibitory effects of deltamethrin, DDT, and GH414. GH266 and GH149 also caused a dramatic enhancement of [3H]muscimol binding, 367 and 236% of control, respectively, whereas DDT and deltamethrin caused only a moderate enhancement. The effects of the insecticides on binding affinity and density were examined for each of the ligands. The results show a differential interaction of the insecticides on the various ligand binding sites.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000378:metabolism; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D007476:Ionophores / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007306:Insecticides; D007476:Ionophores; D009570:Nitriles; D011722:Pyrethrins; D011963:Receptors, GABA-A; D009118:Muscimol; C017180:decamethrin; C037476:tert-butylbicyclophosphorothionate; D003634:DDT; D003975:Diazepam