COMPARISON OF LINDANE, BICYCLOPHOSPHATE AND PICROTOXIN BINDING TO THE PUTATIVE CHLORIDE CHANNEL SITES IN RAT-BRAIN AND TORPEDO ELECTRIC ORGAN

The relative potencies of lindane, picrotoxin and several bicyclophosphate derivatives were compared in their ability to compete with 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in membranes derived from Torpedo electric organ and rat brain. Lindane proved to be ten times more potent in competing with 35S-TBPS binding in electric organ than rat brain, while the bicyclophosphate analogs displayed up to three orders of magnitude greater affinity for rat brain over electric organ. GABA inhibited 35S-TBPS binding in rat brain with moderate potency (IC50 = 30 μM), while unlabelled TBPS inhibited the binding of 3H-muscimo to the GABA receptor with an IC50>100 μM. The GABA receptor antagonist bicuculline increased 35S-TBPS binding in rat brain both in the presence and absence of 30 μM GABA. The results of the study are discussed in the context of a pharmacological discrimination between voltage-sensitive and receptor-gated Cl- channels in nervous tissue, with lindane and the i-propylbicyclophosphate derivative being the most selective compounds for discriminating between them. © 1990.