Pharmacology of FMRFamide‐related Peptides in Helminths

Abstract

Nervous systems of helminths are highly peptidergic. Species in the phylum Nematoda (roundworms) possess at least 50 FMRFamide-related peptides (FaRPs), with more yet to be identified. To date, few non-FaRP neuropeptides have been identified in these organisms, though evidence suggests that other families are present. FaRPergic systems have important functions in nematode neuromuscular control. In contrast, species in the phylum Platyhelminthes (flatworms) apparently utilize fewer FaRPs than do nematodes; those species examined possess one or two FaRPs. Other neuropeptides, such as neuropeptide F (NPF), play key roles in flatworm physiology. Although progress has been made in the characterization of FaRP pharmacology in helminths, much remains to be learned. Most studies on nematodes have been done with Ascaris suum because of its large size. However, thanks to the Caenorhabditis elegans genome project, we know most about the FaRP complement of this free-living animal. That essentially all C. elegans FaRPs are active on at least one A. suum neuromuscular system argues for conservation of ligand-receptor recognition features among the Nematoda. Structure-activity studies on nematode FaRPs have revealed that structure-activity relationship (SAR) "rules" differ considerably among the FaRPs. Second messenger studies, along with experiments on ionic dependence and anatomical requirements for activity, reveal that FaRPs act through many different mechanisms. Platyhelminth FaRPs are myoexcitatory, and no evidence exists of multiple FaRP receptors in flatworms. Interestingly, there are examples of cross-phylum activity, with some nematode FaRPs being active on flatworm muscle. The extent to which other invertebrate FaRPs show cross-phylum activity remains to be determined. How FaRPergic nerves contribute to the control of behavior in helminths, and are integrated with non-neuropeptidergic systems, also remains to be elucidated.

Molecular cloning and functional expression of the first insect FMRFamide receptor

“…Since then, FMRFamide and FMRFamide-related peptides have been isolated from a wide variety of invertebrate species, ranging from primitive metazoans, such as cnidarians, to higher invertebrates, such as insects (2)(3)(4)(5). FMRFamide-related peptides occur in all classes of cnidarians, suggesting that these peptides were among the first transmitters used in evolution (6).…”

Functional characterization of the putative orphan neuropeptide G‐protein coupled receptor C26F1.6 in Caenorhabditis elegans

“…Animals in which the coding region of the flp-7 and flp-11 peptide precursor genes has been deleted, neither display an observable phenotype [18]. However, in nematodes in particular, it has been reported that FaRPergic neurons innervate essentially all muscular systems [19]. In Ascaris suum, AMRNALVRFamide induces a shortening of the ovijector, coupled with an increase in contraction frequency [17].…”

“…The C. elegans genome (97 Mb, 19.099 genes in total) codes for about 1000 G-protein coupled receptors (GPCRs) [1]. About 100 of these encode neuropeptide GPCRs [2].…”

Neuromuscular function in plant parasitic nematodes: a target for novel control strategies?

“…The conserved nature of the nematode nervous system means that physiological information gained from this species can be taken as representative of the phylum as a whole. The majority of FLPs tested in A. suum preparations potently modulate nerve and muscle activity in a concentration-dependent and reversible manner and this activity has been the subject of several reviews Geary et al 1999). For example, the FLP KHEYLRFamide produces a biphasic response resulting in increased contractility of body wall muscle at a threshold of 1 pM (Bowman et al 1996).…”