Unusual effects of benzodiazepines and cyclodiene insecticides on an expressed invertebrate GABAA receptor.
We have previously reported [(1991) EMBO J. 10, 3239-3245] the sequence of an invertebrate gamma-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 active 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.
Zaman
S H
SH
MRC Molecular Neurobiological Unit, MRC Centre, Cambridge, UK.
Harvey
R J
RJ
Barnard
E A
EA
Darlison
M G
MG
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004732:Endrin / Q000494:pharmacology; D006534:Heptachlor Epoxide / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D008195:Lymnaea; D010852:Picrotoxin / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
D001569:Benzodiazepines; D001570:Benzodiazepinones; D003975:Diazepam; D004732:Endrin; D006534:Heptachlor Epoxide; D007306:Insecticides; D010852:Picrotoxin; D012313:RNA; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam