The Interaction of Chlorinated Alicyclic Insecticides with Brain GabaA Receptors in Channel Catfish (Ictalurus Punctatus)

Abstract

Chlorinated alicyclic insecticides are believed to antagonize the action of the neurotransmitter γ-aminobutyric acid (GABA) at its receptor in vertebrates. Binding of the specific GABAA 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 α-chlordane, and oxychlordane were intermediate in potency (122-219 nM), as were isodrin, dihydroisodrin, heptachlor epoxide, and α-chlordane, which were similar in potency (311-397 nM). Dieldrin, lindane, and dihydroaldrin were much less potent (592-1103 nM). Heptachlor, aldrin, and γ-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 μM. 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.