A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus
Haemonchus contortus is a blood feeding parasitic nematode infecting ruminants causing anemia and poor health at great economic cost. The ability to pharmaceutically control infection has been challenged by the rapid development and spread of drug resistance. The discovery of new targets is therefor...
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ndltd-LACETR-oai-collectionscanada.gc.ca-OOSHDU.10155-2982013-04-17T04:05:44ZA molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortusKaji, MarkHaemonchus contortusGABAA agonistsGABAA receptorsHomology modellingCys-loop receptorsHaemonchus contortus is a blood feeding parasitic nematode infecting ruminants causing anemia and poor health at great economic cost. The ability to pharmaceutically control infection has been challenged by the rapid development and spread of drug resistance. The discovery of new targets is therefore required for sustainable parasite control. UNC-49 is a nematode ligand-gated ion channel that plays an important role in muscle contraction required for normal locomotion. However, little is known regarding its sensitivity to different agonists and how they interact with the binding site. This thesis describes an investigation into the efficacy of a range of classical GABA receptor agonists on Hco-UNC-49 expressed in Xenopus oocytes. The results of our electrophysiological recordings indicate that there is a size requirement for full agonism of the Hco-UNC-49 binding site. Furthermore, a number of molecules that are known to act on vertebrate GABA receptors have no effect on Hco-UNC-49. This suggests that the binding site of nematode GABA receptors does exhibit some unique properties. These findings could possibly be exploited to develop new drugs that specifically target GABA receptors from parasitic nematodes.UOITForrester, Sean2013-01-18T16:35:24Z2013-01-18T16:35:24Z2012-11-01Thesishttp://hdl.handle.net/10155/298en |
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en |
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Haemonchus contortus GABAA agonists GABAA receptors Homology modelling Cys-loop receptors |
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Haemonchus contortus GABAA agonists GABAA receptors Homology modelling Cys-loop receptors Kaji, Mark A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
description |
Haemonchus contortus is a blood feeding parasitic nematode infecting ruminants causing anemia and poor health at great economic cost. The ability to pharmaceutically control infection has been challenged by the rapid development and spread of drug resistance. The discovery of new targets is therefore required for sustainable parasite control. UNC-49 is a nematode ligand-gated ion channel that plays an important role in muscle contraction required for normal locomotion. However, little is known regarding its sensitivity to different agonists and how they interact with the binding site. This thesis describes an investigation into the efficacy of a range of classical GABA receptor agonists on Hco-UNC-49 expressed in Xenopus oocytes. The results of our electrophysiological recordings indicate that there is a size requirement for full agonism of the Hco-UNC-49 binding site. Furthermore, a number of molecules that are known to act on vertebrate GABA receptors have no effect on Hco-UNC-49. This suggests that the binding site of nematode GABA receptors does exhibit some unique properties. These findings could possibly be exploited to develop new drugs that specifically target GABA receptors from parasitic nematodes. === UOIT |
author2 |
Forrester, Sean |
author_facet |
Forrester, Sean Kaji, Mark |
author |
Kaji, Mark |
author_sort |
Kaji, Mark |
title |
A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
title_short |
A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
title_full |
A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
title_fullStr |
A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
title_full_unstemmed |
A molecular characterization of agonists that bind to Hco-UNC-49, a GABA-gated chloride channel from Haemonchus contortus |
title_sort |
molecular characterization of agonists that bind to hco-unc-49, a gaba-gated chloride channel from haemonchus contortus |
publishDate |
2013 |
url |
http://hdl.handle.net/10155/298 |
work_keys_str_mv |
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