Glutamate binding studies on membrane preparations from unselected and ivermectin-selected strains of the parasitic nematode of ruminants, Haemonchus contortus, indicated a single class of saturable, high affinity binding sites which are sensitive to ivermectin and exhibit different pharmacological characteristics from any known mammalian glutamate receptor. These studies showed that H. contortus larvae possess substantially more glutamate binding sites with lower affinity than adults. Moreover, selection with ivermectin was associated with an increase in the number of glutamate binding sites in adults and an increase in the affinity for glutamate binding in larvae. When investigating the effects of ivermectin on glutamate binding kinetics, it was discovered that ivermectin decreased Bmax values in unselected, but not in ivermectin-selected, parasites. Inulin intake studies were performed in unselected and ivermectin-selected H. contortus worms to relate the glutamate binding results to the biological activity, pharyngeal pumping. These studies showed that glutamate, ivermectin and the structurally similar anthelmintic, moxidectin, inhibit pharyngeal pumping, and that glutamate influences the effects of ivermectin and of moxidectin, on pharyngeal pumping. Lastly, selection with ivermectin was associated with an alteration of the effects of ivermectin, but not moxidectin, on pharyngeal pumping. The results of this work suggest that a novel ivermectin-sensitive, glutamate receptor, which influences pharyngeal function, is involved in the development of ivermectin resistance in H. contortus.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20604 |
| Date | January 1998 |
| Creators | Paiement, Jean-Pierre. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Institute of Parasitology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001641775, proquestno: MQ44240, Theses scanned by UMI/ProQuest. |
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