Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin.
Glutamate-gated chloride channels, members of the ligand-gated ion channel superfamily, have been shown in nematodes and in insects to be a target of the antiparasitic agent avermectin. Two subunits of the Caenorhabditis elegans glutamate-gated chloride channel have been cloned: GluCl-alpha and GluCl-beta. We report the cloning of a Drosophila melanogaster glutamate-gated chloride channel, DrosGluCl-alpha, which shares 48% amino acid and 60% nucleotide identity with the C. elegans GluCl channels. Expression of DrosGluCl-alpha in Xenopus oocytes produces a homomeric chloride channel that is gated by both glutamate and avermectin. The DrosGluCl-alpha channel has several unique characteristics not observed in C. elegans GluCl: dual gating by avermectin and glutamate, a rapidly desensitizing glutamate response, and a lack of potentiation of the glutamate response by avermectin. The pharmacological data support the hypothesis that the DrosGluCl-alpha channel represents the arthropod H-receptor and an important target for the avermectin class of insecticides.
Cully
D F
DF
Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA.
Paress
P S
PS
Liu
K K
KK
Schaeffer
J M
JM
Arena
J P
JP
D000818:Animals; D001483:Base Sequence; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004331:Drosophila melanogaster / Q000502:physiology*; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D015870:Gene Expression; D017344:Genes, Insect; D005971:Glutamates / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D017470:Receptors, Glutamate / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
D065101:Chloride Channel Agonists; D018118:Chloride Channels; D017931:DNA Primers; D018690:Excitatory Amino Acid Agonists; D005971:Glutamates; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D007559:Ivermectin; C019264:avermectin