FMRFamide-related peptides (FaRPs) in nematodes: occurrence and neuromuscular physiology

Abstract

The occurrence of classical neurotransmitter molecules and numerous peptidic messenger molecules in nematode nervous systems indicate that although structurally simple, nematode nervous systems are chemically complex. Thus far, studies on one nematode neuropeptide family, namely the FMRFamide-related peptides (FaRPs), have revealed an unexpected variety of neuropeptide structures in both free-living and parasitic species. To date 23 nematode FaRPs have been structurally characterized including 12 from Ascaris suum, 8 from Caenorhabditis elegans, 5 from Panagrellus redivivus and 1 from Haemonchus contortus. Ten FaRP-encoding genes have been identified in Caenorhabditis elegans. However, the full complement of nematode neuronal messengers has yet to be described and unidentified nematode FaRPs await detection. Preliminary characterization of the actions of nematode neuropeptides on the somatic musculature and neurones of A, suum has revealed that these peptidic messengers have potent and complex effects. Identified complexities include the biphasic effects of KNEFIRFamide/KHEYLRFamide (AF1/2; relaxation of tone followed by oscillatory contractile activity) and KPNFIRFamide (PF4; rapid relaxation of tone followed by an increase in tone), the diverse actions of KSAYMRFamide (AF8 or PF3; relaxes dorsal muscles and contracts ventral muscles) and the apparent coupling of the relaxatory effects of SDPNFLRFamide/SADPNFLRFamide (PF1/PF2) to nitric oxide release. Indeed, all of the nematode FaRPs which have been tested on somatic muscle strips of A. suum have actions which are clearly physiologically distinguishable. Although we are a very long way from understanding how the actions of these peptides are co-ordinated, not only with those of each other but also with those of the classical transmitter molecules, to control nematode behaviour, their abundance coupled with their diversity of structure and function indicates a hitherto unidentified sophistication to nematode neuromuscular intergration.

Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum

“…It is interesting that peptide AF8 (encoded by afp-3 [32]), which was tested previously [28], also produces ventral coils, but since AF8, unlike AF30, does not change cAMP levels, we conclude that ventral coiling does not necessarily involve changes in cAMP. AF8 (KSAYMRFa) has been shown to relax dorsal muscle and contract ventral muscle [46], consistent with the generation of ventral coils. It may be relevant that both AF8 and AF30 share a C-terminal –MRFa sequence.…”

Neuropeptides

“…Similarly, application of peptides encoded by 20 flp genes had a range of effects on body wall, reproductive, and pharyngeal muscle of Ascaris suum (Fellowes et al, 1998; Bowman et al, 2002; Moffett et al, 2003; Trailovic et al, 2005; for reviews see Maule et al, 1996; Brownlee et al, 1996; Brownlee and Walker, 1999; Brownlee et al, 2000), and it is likely that these FLPs have similar effects in C. elegans . On Ascaris muscle, different FLPs can activate different ion channels.…”

A review of FMRFamide- and RFamide-like peptides in metazoa

“…Some of these effects are presynaptic on motoneuron terminals since AF2 potentiated excitatory junctional potentials (ejps) recorded from the muscle cells but AF2 did not potentiate the effect of muscle depolarization due to bath-applied acetylcholine (Pang et al 1995). Maule et al have also conducted extensive studies on the bioactivity of FLPs (Maule et al , 1996Mousley et al 2005). The PF FLPs identified in Panagrellus redivivus are of particular interest (Geary et al 1992;Maule et al 1995).…”