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L-Glutamate binding sites of parasitic nematodes: an association with ivermectin resistance?


Reference:

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.

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Abstract

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.

Details

Item Type Articles
CreatorsHejmadi, M. V., Jagannathan, S., Delany, N. S., Coles, G. C. and Wolstenholme, A. J.
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code4437
Additional InformationID number: ISI:000087528500011

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