Inhibitory amine neurotransmission in parasitic nematodes

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Dopamine and serotonin are neurotransmitters that play important roles in the function of the mammalian central nervous system. Primitive organisms such as nematodes also utilize dopamine and serotonin. However, in nematodes, these molecules appear to have different functions and, perhaps more intriguingly, act on unique receptors from the ligand-gated chloride channel family. These channels have been identified in the free-living nematode Caenorhabditis elegans and recently, by our group, in the parasitic nematode Haemonchus contortus. Both C. elegans and H. contortus are genetically related nematode species. However, they exhibit extreme differences in their size, nutrition and overall lifestyle. H. contortus is blood-feeding parasite that infects cattle, sheep and goats world-wide while C. elegans is a bacteria-feeding soil nematode. The long-term goal of our research is to determine how the nervous system of parasitic nematodes may relate specifically to their life-style. This proposal will investigate the function of serotonin- and dopamine-activated chloride channels in the nervous system of the parasitic nematode H. contortus. Our approach is to determine where in the parasite serotonin and dopamine molecules are released and relate this information to the location and function of the channels that bind these molecules. This will provide important information on the overall function of dopamine and serotonin chloride channels in parasitic nematodes and will provide the foundation for a comparison between the function of these channels in parasitic verses free-living nematodes. This will significantly enhance our understanding of parasitism. Furthermore, since these channels appear to be unique to nematodes, they may be identified, in the future, as attractive targets for the next generation of anti-parasitic drugs. This will have important implications for the control of parasites that are important to Canada.