Structure and Function of Ascaris Neuropeptides

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The locomotory system of nematodes is the target of many currently used anthelminthics, since disruption of locomotory behavior interferes with the normal processes by which many nematodes maintain their position within the host. The problem of genetic drug resistance is making many of the available drugs less effective, so it is important to develop new generations of anti-nematdde drugs. The proposed research aims to describe new intercellular signaling systems that are important in the motornervous system that controls locomotion. Our strategy is based on our previous work in which we isolated and sequenced a large family of 29 novel endogenous neuropeptides in the parasitic nematode, Ascaris suum. Preliminary experiments have shown that almost all of the peptides tested have potent activity .on the neuromuscular system of Ascaris. Some cause paralysis, others exaggerate locomotory movements. Neuropeptides, therefore, play an important role in the overall activity of the motornervous system. There is every indication that there are many more peptides than the ones we have isolated so far. There is no indication that the currently available peptides are the most potent, so we propose to isolate new peptides, concentrating on those that are present in the motornervous system, in order to detect new peptides that have potent physiological activity. This is basic research upon which new generations of anthelminthics can ultimately be developed.