Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans.

Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
The FASEB Journal (Impact Factor: 5.48). 09/2008; 22(9):3247-54. DOI: 10.1096/fj.08-110502
Source: PubMed

ABSTRACT Sydney Brenner promoted Caenorhabditis elegans as a model organism, and subsequent investigations pursued resistance to the nicotinic anthelmintic drug levamisole in C. elegans at a genetic level. These studies have advanced our understanding of genes associated with neuromuscular transmission and resistance to the antinematodal drug. In lev-8 and lev-1 mutant C. elegans, levamisole resistance is associated with reductions in levamisole-activated whole muscle cell currents. Although lev-8 and lev-1 are known to code for nicotinic acetylcholine receptor (nAChR) subunits, an explanation for why these currents get smaller is not available. In wild-type adults, nAChRs aggregate at neuromuscular junctions and are not accessible for single-channel recording. Here we describe a use of LEV-10 knockouts, in which aggregation is lost, to make in situ recordings of nAChR channel currents. Our observations provide an explanation for levamisole resistance produced by LEV-8 and LEV-1 mutants at the single-channel level.

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    ABSTRACT: The aim of the present study was to analyze the effectiveness of levamisole and trichlorphon in controlling intestinal capilariasis in zebrafish. Various protocols of treatment against this parasite were successively tested. Fish (280 g ± 53 g) were randomly assigned to 3 experiments. In experiment I, fish (n = 160) were administered levamisole at 1 mg/L (group 1), 2 mg/L (group 2), 5 mg/L (group 3), and 10 mg/L (group 4), by 72 h bath. In experiment II, fish (n = 160) were administered levamisole by bath (as in experiment I) and per os at 200 mg/100g diet twice a day for 3 days. In experiment III, fish (n = 160) were administered levamisole by bath (as in experiment I) and trichlorphon per os at 0.2 mg/100 g diet twice a day for 3 days. These schemes of treatment were repeated at days 7 and 14. At the beginning of treatment,100% of fish were infested by Capillariinae. The mean abundance was estimated at 3.5 (range of intensity: 2-5). In experiments I and II, 21 days after the beginning of treatment, fish were still infested by live parasites. However, with the highest dose of levamisole, the mean abundance of invasion decreased to 0.8 (range of intensity: 0-3) in experiment I, and to 0.3 (range of intensity: 0-2) in experiment II – a reduction of 73.33% and 90.00%, respectively. The combined treatment in experiment III (levamisole by bath and trichlorphon per os) was the most effective. Only in experiment III were parasites eliminated after 14 days in groups 2 and 3, and after 21 days in groups 1, 2, 3 and 4. These results suggest that a combination of levamisole and trichlorphon could be an effective alternative for the control of nematode zebrafish infections, including those by levamisole-resistant strains.
    Medycyna weterynaryjna 04/2015; 74(4):245-250. · 0.20 Impact Factor
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    Dataset: emodepide