Noncompetitive inhibition of GABA receptors in insect and vertebrate CNS by endrin and lindane

Abstract

γ-Aminobutyric acid (GABA) receptors have been recognized as a possible primary site of action for polychlorocycloalkane insecticides (cyclodienes and cyclohexanes). The mechanism of action of endrin and lindane on functional insect central nervous system (CNS) GABA receptors was studied by applying electrophysiological techniques to the cell body of an identified motor neuron, the fast coxal depressor motor neuron ( D f) of the cockroach Periplaneta americana. The technique of monitoring GABA-regulated 36 Cl − influx into rat brain membranes, which provides a functional assay for vertebrate CNS GABA A receptors, was also used to study the actions of these two polychlorocycloalkane insecticides. Endrin and lindane inhibited in a dose-dependent, noncompetitive manner both insect and vertebrate GABA receptors. Lindane was at least an order of magnitude less potent than endrin. The results demonstrate that endrin and lindane act in a similar manner on the GABA receptors of both insect and mammalian central nervous systems. Their blocking actions may involve noncompetitive binding to an allosteric site associated with the receptor's chloride channel. Toxicity of these insecticides to both vertebrates and insects appears to be mediated by their inhibitory actions on GABA receptors.