NEMATODE FMRFAMIDE-RELATED PEPTIDE (FARP)-SYSTEMS - OCCURRENCE, DISTRIBUTION AND PHYSIOLOGY

The application of rational (mechanism-based) approaches to anthelmint ic discovery requires information about target proteins which are phar macologically distinguishable from their vertebrate homologs. In helmi nths, several such targets (e.g., beta-tubulin, ATP-generating enzymes , cholinergic receptors, Cl- channels) have been characterized only af ter the discovery, through empirical screening, of compounds that inte rfere with their function. From the perspective of anthelmintic discov ery, the utility of these targets is diminishing due to the emergence of drug-resistant strains of parasites. This has motivated the search for compounds with novel modes-of-action. Recent basic research in hel minth physiology and biochemistry has identified several potential tar gets for rational anthelmintic discovery, including receptors for FMRF amide-related peptides (FaRPs). To date, over 20 different nematode Fa RPs have been identified and these peptides, which are broadly distrib uted in helminths, have been localized to all of the major neuronal su btypes in nematodes. The FaRPs that have been examined have been found profoundly to affect somatic muscle function in gastrointestinal nema todes. In this respect, complex inhibitory and excitatory actions have been identified for a number of these peptides. Although the transduc tion pathways for any of these peptides remain to be elucidated, the a vailable evidence indicates that nematode FaRPs have numerous mechanis ms of action. The employment of nematode neuropeptide receptors in mec hanism-based screens has' immense potential in the identification of n ovel anthelmintics. Copyright (C) 1996 Australian Society for Parasito logy. Published by Elsevier Science Ltd.