Structure and bioactivity of neuropeptide F from the human parasites Schistosoma mansoni and Schistosoma japonicum

The blood flukes Schistosoma mansoni and Schistosoma japonicum inflict immense suffering as agents of human schistosomiasis. Previous investigations have found the nervous systems of these worms contain abundant immunoreactivity to antisera targeting invertebrate neuropeptide Fs (NPFs) as well as structurally similar neuropeptides of the mammalian neuropeptide Y (NPY) family. Here, cDNAs encoding NPF in these worms were identified, and the mature neuropeptides from the two species differed by only a single amino acid. Both neuropeptides feature the characteristics common among NPFs; they are 36 amino acids long with a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide and Tyr residues at positions 10 and 17 from the carboxyl terminus. Synthetic S. mansoni NPF potently inhibits the forskolin-stimulated accumulation of cAMP in worm homogenates, with significant effects at 10(-11) M. This is the first demonstration of an endogenous inhibition of cAMP by an NPF, and because this is the predominant pathway associated with vertebrate NPY family peptides, it demonstrates a conservation of downstream signaling pathways used by NPFs and NPY peptides.

The FLP-side of nematodes.

The central role of FMRFamide-like peptides (FLPs) in nematode motor and sensory capabilities makes FLP signalling an appealing target for new parasiticides. Accumulating evidence has revealed an astounding level of FLP sequence conservation and diversity in the phylum Nematoda, and preliminary work has begun to identify the nematode FLP receptor complement in Caenorhabditis elegans, with a view to investigating their basic biology and therapeutic potential. However, much work is needed to clarify the functional aspects of FLP signalling and how these peptides exert their effects at the organismal level. Here, we summarize our current knowledge of nematode FLP signalling.