The interaction of chlorinated alicyclic insecticides with brain GABA(A) receptors in channel catfish (Ictalurus punctatus)

Chlorinated alicyclic insecticides are believed to antagonize the action of the neurotransmitter gamma-aminobutyric acid (GABA) at its receptor in ver tebrates. Binding of the specific GABA(A) receptor ligand [S-35]-t-butylbic yclophosphorothionate (TBPS) to channel catfish brain P-2 membranes suggest ed a single population of receptors with a K-d (56.6 +/- 2.6 nM) and B-max (2435 +/- 276 fmol/mg protein) that are similar to published values for oth er 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-chlo rdane, and oxychlordane were intermediate in potency (122-219 nM), as were isodrin, dihydroisodrin, heptachlor epoxide, and alpha-chlordane, which wer e similar in potency (311-397 nM). Dieldrin, lindane, and dihydroaldrin wer e much less potent (592-1103 nM). Heptachlor, aldrin, and gamma-chlordane w ere weak inhibitors of TBPS binding (2073-2738 nM). Chlordene and chlordeco ne had the lowest potency of all compounds studied (10,201-21,178 nM) with the exception or mirex which did not inhibit binding at a concentration of 50 mu M. There is a good correlation between binding potency and the availa ble toxicity data for several of these compounds in channel catfish. There is also a good correlation between the inhibitory potency in channel catfis h by these types of compounds with that in rats.