REGULATION OF PHARYNGEAL PUMPING IN PARASITIC NEMATODES

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Filarids, hookworms and a variety of intestinal nematodes infect billions of individuals worldwide, while nematode parasites of domesticated animals and cultivated plants have a multibillion dollar impact on the anti-nematodal drug in use today the future direction of nematode chemotherapy is uncertain. Clearly, new contraction are essential processes in all nematodes and serotonin (5-HT) receptors play a key role in the regulation of both, the present study was designed to identify and characterize 5-HT receptors in the parasitic nematode Ascaris suum. Specifically, putative 5-HT receptors from pharynx and body wall muscle will be identified using RT-PCR with degenerate oligonucleotides designed against conserved regions of 5-HT receptors from other organisms and cDNA pools prepared from poly A+RNA isolated from A. suum pharynx and body wall muscle. Then, the putative 5-HT receptors, especially the recently identified 5-HT2-like receptor isoforms, will be functionally expressed in mammalian cell lines and the pharmacology and coupling of the wall muscle and 5-HT dependent changes in adenyl cyclase activity, phosphoinositide turnover and pharyngeal pumping in physiological preparations of A. suum pharynx or body wall muscle. These studies should generate a clear description of the role of 5-HT receptors in the regulation of pharyngeal pumping and muscle contraction/metabolism in nematodes and should provide an excellent framework for the development of specific inhibitors of these essential processes.