L-Glutamate binding sites of parasitic nematodes: an association with ivermectin resistance?
Hejmadi, M. V., Jagannathan, S., Delany, N. S., Coles, G. C. and Wolstenholme, A. J., 2000. L-Glutamate binding sites of parasitic nematodes: an association with ivermectin resistance? Parasitology, 120, pp. 535-545.
Related documents:This repository does not currently have the full-text of this item.
You may be able to access a copy if URLs are provided below.
Nematode membrane preparations contain high amounts of low-affinity specific L-glutamate binding sites. The numbers of these sites were increased in 2 isolates, one field-derived and the other laboratory-derived, of ivermectin-resistant Haemonchus contortus and a field isolate of ivermectin-resistant Telodorsagia circumcincta, when compared to control, drug-sensitive isolates. Specific [H-3]ivermectin binding to these membrane preparations showed no differences between ivermectin-sensitive and resistant isolates and the number of ivermectin binding sites was approximately 100-fold less than the number of L-glutamate binding sites. Kinetic analysis of L-glutamate binding suggested the presence of at least 2 classes of binding site. L-Glutamate binding was blocked by ibotenic acid, kynurenic acid and beta-hydroxyaspartate, but not by ivermectin, argiopine, kainate, quisqualate or NMDA. Competition assays with ibotenic acid suggested that there were 2 distinct populations of glutamate binding sites and that the site with the lower affinity for ibotenate was upregulated in the ivermectin-resistant nematodes. In the field isolate of resistant H. contortus we found no coding changes in the cDNAs encoding glutamate-gated chloride channel subunits HG2, HG3 and HG4, nor were any changes in channel expression detected using subunit-specific antibodies. The low-affinity binding site is unlikely to be associated with the ivermectin receptor in these nematodes.
|Creators||Hejmadi, M. V., Jagannathan, S., Delany, N. S., Coles, G. C. and Wolstenholme, A. J.|
|Departments||Faculty of Science > Biology & Biochemistry|
|Additional Information||ID number: ISI:000087528500011|
Actions (login required)