In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 25 ( 2000-12-05), p. 13949-13954
Abstract:
The fruit fly Drosophila melanogaster was used to
examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected
by stepwise increasing the dose of drug in the culture media. The resistant strain, glc 1 , is at least 20-fold
resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased
locomotion, and bang sensitivity. Binding assays using glc 1 head membranes showed a marked decrease
in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S)
in the gene coding for the glutamate-gated chloride channel subunit DmGluClα. To examine the effect of this mutation on the biophysical
properties of DmGluClα channels, it was introduced into a recombinant DmGluClα, and RNA encoding wild-type and mutant subunits was injected
into Xenopus oocytes. Nodulisporic acid directly
activated wild-type and mutant DmGluClα channels. However, mutant channels were ≈10-fold less sensitive to activation by nodulisporic
acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and
ivermectin act on DmGluClα channels.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.240464697
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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