Polychlorinated Convulsant Insecticides Potentiate the Protective Effect of NaCl Against Heat Inactivation of [3H]Flunitrazepam Binding Sites

Publisher Website
Google Scholar
Abstract
Six polychlorinated convulsant insecticides that potentaly inhibit t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes also potentiate the protective effect of NaCl (200 mM) against heat inactivation of [3H]flunitrazepam binding sites on the same membranes. Similar effects were obtained with all "cage" convulsants tested. The rank order of potencies as heat protection potentiators was similar to the rank order of potencies as inhibitors of [35S]TBPS binding (.alpha.-endosulfan > endrin > dieldrin > toxaphene > lindane). .alpha.-Endosulfan and endrin are more potent in both respects than any previously reported picrotoxin-like (cage) convuslant, but are much less toxic to mammals. The greatly reduced toxicities of .alpha.-endosulfan and endrin in mammals may reflect partial .gamma.-aminobutyric (GABA)-neutral properties of these compounds. Time courses of heat inactivation of [3H]flunitrazepam binding sites in the presence of 200 mM NaCl plus saturating concentrations of endrin or picrotoxin revealed monophasic components consitituting about 88% of the bindign sites, suggesting that virtually all [3H]flunitrazepam binding sites are coupled to picrotoxin binding sites in the GABA/benzodiazepine/picrotoxin receptor complex. Protection against heat inactivation constitutes a useful tool for characterizing the various allosterically linked binding sites in neurotransmitter receptor complexes.