Abstract
Ivermectin exerts its anthelmintic effect by activating nematode Cys-loop glutamate-gated receptors. Here we show that a glycine residue at a specific transmembrane domain location is essential for high ivermectin sensitivity in both glycine- and glutamate-gated Cys-loop receptors. We also show that ivermectin sensitivity can be conferred on an ivermectin-insensitive receptor by introducing a glycine at this position. Furthermore, comparison of amino acid sequences of ivermectin-sensitive and -resistant receptors reveals that the presence of a glycine reliably predicts ivermectin sensitivity. By providing a means of identifying ivermectin-sensitive receptors, this finding should help in characterising ivermectin-resistance mechanisms and identifying new anthelmintic targets.
| Original language | English |
|---|---|
| Journal | International Journal for Parasitology |
| Volume | 40 |
| Issue number | 13 |
| Pages (from-to) | 1477-1481 |
| Number of pages | 5 |
| ISSN | 0020-7519 |
| DOIs | |
| Publication status | Published - 1 Nov 2010 |
Keywords
- Anthelmintic
- Binding site
- Chloride channel
- Glutamate receptor
- Glycine receptor
- Macrocyclic lactone
- Nematode