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

FEBS Letters

Barnard, Eric A.¹  Darlison, Mark G.¹  Harvey, Robert J.¹  Zaman, Shahid H.¹ 

[1] MRC Molecular Neurobiological Unit, MRC Centre, Hills Road, Cambridge, CB2 2QH, UK

关键词: Benzodiazepine;    Channel blocker;    Cyclodiene insecticide;    Invertebrate;    Lymnaea stagnalis;    GABAA receptor;    Receptor activation;    Xenopus oocyte expression;    cDNA;    complementary DNA;    DMSO;    dimethyl sulphoxide;    GABA;    γ-aminobutyric acid;    PTX;    picrotoxin;    V h;    holding potential;   

DOI  :  10.1016/0014-5793(92)80711-O

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have previously reported [(1991) EMBO J. 10, 3239–3245] the sequence of an invertebrate γ-aminobutyric acid (GABA) type A (GABA_A) 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.

【 授权许可】

Unknown