title: The interaction of chlorinated alicyclic insecticides with brain GABA(A) receptors in channel catfish (Ictalurus punctatus).
abstract: Chlorinated alicyclic insecticides are believed to antagonize the action of the neurotransmitter gamma-aminobutyric acid (GABA) at its receptor in vertebrates. Binding of the specific GABA(A) receptor ligand [35S]-t-butylbicyclophosphorothionate (TBPS) to channel catfish brain P2 membranes suggested a single population of receptors with a Kd (56.6+/-2.6 nM) and Bmax (2435+/-276 fmol/mg protein) that are similar to published values for other fish species. The competition of several chlorinated compounds for TBPS binding was investigated. The most potent inhibitors of TBPS binding were 12-ketoendrin, photoheptachlor epoxide, photoheptachlor, telodrin, and endrin, respectively, with IC50s of 20-90 nM. Photooxychlordane, photo alpha-chlordane, and oxychlordane were intermediate in potency (122-219 nM), as were isodrin, dihydroisodrin, heptachlor epoxide, and alpha-chlordane, which were similar in potency (311-397 nM). Dieldrin, lindane, and dihydroaldrin were much less potent (592-1103 nM). Heptachlor, aldrin, and gamma-chlordane were weak inhibitors of TBPS binding (2073-2738 nM). Chlordene and chlordecone had the lowest potency of all compounds studied (10,201-21,178 nM) with the exception of mirex, which did not inhibit binding at a concentration of 50 microM. There is a good correlation between binding potency and the available toxicity data for several of these compounds in channel catfish. There is also a good correlation between the inhibitory potency in channel catfish by these types of compounds with that in rats.
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D004492:Edetic Acid / Q000378:metabolism; D058787:GABA-A Receptor Antagonists; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism* / Q000633:toxicity*; D007059:Ictaluridae / Q000378:metabolism*; D007306:Insecticides / Q000378:metabolism* / Q000633:toxicity*; D007700:Kinetics; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D054830:Sesterterpenes; D013462:Sulfur Radioisotopes