Unusual effects of benzodiazepines and cyclodiene insecticides on an expressed invertebrate GABAA receptor

Abstract
We have previously reported [(1991) EMBO J. 10, 3239–3245] the sequence of an invertebrate γ‐aminobutyric acid (GABA) type A (GABAA) receptor polypeptide which forms homo‐oligomeric GABA‐gated, bicuculline‐sensitive, chloride‐ion channels upon heterologous expression. We now demonstrate that the benzodiazepines Ro5‐4864 (4′‐chlorodiazepam) and diazepam, that are active at mammalian peripheral benzodiazepine sites, and not those benzodiazepines specific for central sites, directly activate the homo‐oligomeric receptor and evoke larger maximal responses than those elicited by GABA. In addition, members of the cyclodiene class of insecticides block the channel of the receptor in a manner indistinguishable from that of picrotoxin.