Allosteric modulation by benzodiazepines of GABA-gated chloride channels of an identified insect motor neurone.
The actions of benzodiazepines were studied on the responses to GABA of the fast coxal depressor (D(f)) motor neurone of the cockroach, Periplaneta americana. Ro5-4864, diazepam and clonazepam were investigated. Responses to GABA receptors were enhanced by both Ro5-4864 and diazepam, whereas clonazepam, a potent-positive allosteric modulator of human GABA(A) receptors, was ineffective on the native insect GABA receptors of the D(f) motor neurone. Thus, clear pharmacological differences exist between insect and mammalian native GABA-gated chloride channels with respect to the actions of benzodiazepines. The results enhance our understanding of invertebrate GABA-gated chloride channels which have recently proved important in (a) comparative studies aimed at identifying human allosteric drug-binding sites and (b) understanding the actions of compounds used to control ectoparasites and insect crop pests.
MRC Functional Genomics Unit, Department of Physiology Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. steven.buckingham@dpag.ox.ac.uk
Steven D
SD
Buckingham
Yoshiaki
Y
Higashino
David B
DB
Sattelle
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism*; D002998:Clonazepam / Q000008:administration & dosage / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D010526:Periplaneta; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001570:Benzodiazepinones; D018118:Chloride Channels; D018757:GABA Modulators; D019476:Insect Proteins; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam; D003975:Diazepam