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

Published online by Cambridge University Press:  06 April 2009

A. G. Maule*
Affiliation:
Comparative Neuroendocrinology Research Group, School of Biology and Biochemistry and Clinical Medicine, The Queen's University of Belfast, Belfast BT7 INN, Northern Ireland
J. W. Bowman
Affiliation:
Animal Health Discovery Research, Pharmacia and Upjohn Incorporated, 301 Henrietta Street, Kalamazoo, MI 49001, USA
D. P. Thompson
Affiliation:
Animal Health Discovery Research, Pharmacia and Upjohn Incorporated, 301 Henrietta Street, Kalamazoo, MI 49001, USA
N. J. Marks
Affiliation:
Comparative Neuroendocrinology Research Group, School of Biology and Biochemistry and Clinical Medicine, The Queen's University of Belfast, Belfast BT7 INN, Northern Ireland
A. R. Friedman
Affiliation:
Animal Health Discovery Research, Pharmacia and Upjohn Incorporated, 301 Henrietta Street, Kalamazoo, MI 49001, USA
T. G. Geary
Affiliation:
Animal Health Discovery Research, Pharmacia and Upjohn Incorporated, 301 Henrietta Street, Kalamazoo, MI 49001, USA
*
*Corresponding author:

Summary

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.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Atkinson, H. J., Isaac, R. E., Harris, P. D. & Sharpe, C. M. (1988). FMRFamide-immunoreactivity within the nervous system of the nematodes Panagrellus redivivus, Caenorhabditis elegans and Heterodera glycines. Journal of Zoology London 216, 663–71.CrossRefGoogle Scholar
Bascal, Z. A., Montgomery, A., Holden-Dye, L., Williams, R. G., Thorndyke, M. C. & Walker, R. J. (1995). Histochemical mapping of NADPH diaphorase in the nervous system of the parasitic nematode, Ascaris suum. Parasitology 110, 625–37.CrossRefGoogle Scholar
Benjamin, P. R. & Burke, J. F. (1994). Alternative mRNA splicing of the FMRFamide gene and its role in neuropeptidergic signaling in a defined neural network. BioEssays 16, 335–42.CrossRefGoogle Scholar
Bowman, J. W., Friedman, A. R., Thompson, D. P., Ichhpurani, A. K., Kellman, M. F. & Geary, T. G. (1996). Structure-activity relationships in a nematode FMRFamide-like peptide, KNEFIRFamide. Peptides 17, 381–7.CrossRefGoogle Scholar
Bowman, J. W., Geary, T. G. & Thompson, D. P. (1990). Electrophysiological characterization of the effects of nematode FMRFamide-like neuropeptides on Ascaris suum muscle cells. Neurotox ”90 Abstracts, 129.Google Scholar
Bowman, J. W., Winterrowd, C. A., Friedman, A. R., Thompson, D. P., Klein, R. D., Davis, J. P., Maule, A. G. & Geary, T. G. (1995). Nitric oxide mediates the inhibitory effects of SDPNFLRFamide, a nematode FMRFamide-like neuropeptide, in Ascaris suum. Journal of Neurophysiology 74, 1880–8.CrossRefGoogle Scholar
Brownlee, D. J. A., Brennan, G. P., Halton, D. W., Fairweather, I. & Shaw, C. (1994b). Ultrastructural localisation of pancreatic polypeptide- and FMRFamide-immunoreactivities within the central nervous system of the nematode, Ascaris suum (Nematoda, Ascaroidea). Parasitology 108, 587–93.Google ScholarPubMed
Brownlee, D. J. A., Fairweather, I. & Johnston, C. F. (1993 a). Immunocytochemical demonstration of neuropeptides in the peripheral nervous system of the roundworm Ascaris suum (Nematoda, Ascaroidea). Parasitology Research 79, 302–8.CrossRefGoogle Scholar
Brownlee, D. J. A., Fairweather, I., Johnston, C. F. & Shaw, C. (1994a). Immunocytochemical demonstration of peptidergic and serotoninergic components in the enteric nervous system of the roundworm, Ascaris suum (Nematoda, Ascaroidea). Parasitology 108, 89103.CrossRefGoogle Scholar
Brownlee, D. J. A., Fairweather, I., Johnston, C. F., Smart, D., Shaw, C. & Halton, D. W. (1993 b). Immunocytochemical demonstration of neuropeptides in the central nervous system of the roundworm Acaris suum (Nematoda, Ascaroidea). Parasitology 106, 305–16.CrossRefGoogle Scholar
Brownlee, D. J. A., Fairweather, I., Thorndyke, M. C. & Johnston, C. F. (1996). Cellular and subcellular localization of SALMFamide (Sl)-like immunoreactivity within the central nervous system of the nematode Ascaris suum (Nematoda, Ascaroidea). Parasitology Research 82, 149–56.CrossRefGoogle Scholar
Brownlee, D. J. A., Holden-Dye, L., Fairweather, & Walker, R. J.. (1995). The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum. Parasitology 111, 379–84.CrossRefGoogle ScholarPubMed
Cowden, C. & Stretton, A. O. W. (1993). AF2, an Ascaris neuropeptide: Isolation, sequence and bioactivity. Peptides 14, 423–30.CrossRefGoogle ScholarPubMed
Cowden, C. & Stretton, A. O. W. (1995). Eight novel FMRFamide-like neuropeptides isolated from the nematode Ascaris suum. Peptides 16, 491500.CrossRefGoogle Scholar
Cowden, C., Stretton, A. O. W. & Davis, A. E. (1989). AF1, a sequenced bioactive neuropeptide isolated from the nematode Ascaris suum. Neuron 2, 1465–73.CrossRefGoogle Scholar
Cowden, C.Sithigorngul, P., Brackley, P., Guastella, J.. & Stretton, A. O. W. (1993). Localisation and differential expression of FMRFamide immunoreactivity in the nematode Ascaris suum. Journal of Comparative Neurology 333, 455–68.CrossRefGoogle Scholar
Davenport, T. R. B., Lee, D. L. & Isaac, R. E. (1988). Immunocytochemical demonstration of a neuropeptide in Ascaris suum (Nematoda) using an anti- serum to FMRFamide. Parasitology 97, 81–8.CrossRefGoogle Scholar
Davey, K. G. (1966). Neurosecretion and moulting in some parasitic nematodes. American Zoologist 6, 243–9.CrossRefGoogle ScholarPubMed
Del Castillo, J., De Mello, W. C. & Morales, T. (1964a). Influence of some ions on the membrane potential of Ascaris muscle. Journal of General Physiology 48, 129–40.CrossRefGoogle Scholar
Del Castillo, J., De Mello, W. C. & Morales, T. (1964b). Inhibitory action of γ-aminobutyric acid (GABA) on Ascaris muscle. Experientia 20, 141–3.CrossRefGoogle ScholarPubMed
Dockray, G. J., Reeve, J. R., Shively, J., Gayton, R. J. & Barnard, C. S. (1983). A novel active pentapeptide from chicken brain identified by antibodies to FMRFamide. Nature 305, 328–30.CrossRefGoogle ScholarPubMed
Franks, C. J., Holden-Dye, L., Williams, R. G., Pang, F.- Y. & Walker, R. J.. (1994). A nematode FMRFamidelike peptide SDPNFLRFamide (PF1) relaxes the dorsal muscle strip preparation of Ascaris suum. Parasitology 108, 229–36.CrossRefGoogle ScholarPubMed
Geary, T. G., Bowman, J. W., Friedman, A. R., Maule, A. G., Davis, J. P., Winterrowd, C. A., Klein, R.D. & Thompson, D. P. (1995). The Pharmacology of FMRFamide-related neuropeptides in nematodes: New opportunities for rational anthelmintic discovery?. International Journal for Parasitology 25, 1273–80.CrossRefGoogle ScholarPubMed
Geary, T. G., Price, D. A., Bowman, J. W., Winterrowd, C. A., Mackenzie, C. D., Garrison, R. D., Williams, J. F. & Friedman, A. R. (1992). Two FMRFamide-like peptides from the free-living nematode Panagrellus redivivus. Peptides 13, 209–14.CrossRefGoogle ScholarPubMed
Halton, D. W., Shaw, C., Maule, A. G. & Smart, D. (1994). Regulatory peptides in helminth parasites. Advances in Parasitology 34, 164227.Google Scholar
Holden-Dye, L., Franks, C. J., Williams, R. G. & Walker, R. J.. (1995). The effect of the nematode peptides SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2) on synaptic transmission in the parasitic nematode Ascaris suum. Parasitology 110, 449–55.CrossRefGoogle ScholarPubMed
Holman, G. M., Cook, B. J. & Nachman, R. J. (1986). Isolation, primary structure and synthesis of two neuropeptides from Leucophaea maderae: members of a new family of cephalomyotropins. Comparative Biochemistry and Physiology 84C, 205–11.Google Scholar
Jagdale, G. B. & Gordon, R. (1994). Distribution of FMRFamide-like peptide in the nervous system of a mermithid nematode, Romanomermis culicivorax. Parasitology Research 80, 467–73.CrossRefGoogle Scholar
Johnson, C. D. & Stretton, A. O. W. (1987). GABAimmunoreactivity in inhibitory motor neurons of the nematode Ascaris. Journal of Neuroscience 7, 223–35.CrossRefGoogle Scholar
Keating, C., Holden-Dye, L. M. & Walker, R. J. (1996). Investigation of the mode of action of nematode neuropeptides. Pesticide Science 46, 263–6.3.0.CO;2-U>CrossRefGoogle Scholar
Keating, C., Thorndyke, M. C., Holden-Dye, L., Williams, R. G. & Walker, R. J.. (1995). The isolation of a FMRFamide-like peptide from the nematode Haemonchus contortus. Parasitology 111, 515–21.CrossRefGoogle ScholarPubMed
Kerwin, J. F. & Heller, M. (1994). The arginine-nitric oxide pathway: a target for new drugs. Medicinal Research Reviews 14(1), 2374.CrossRefGoogle ScholarPubMed
Kubiak, T. M., Maule, A. G., Marks, N. J., Martin, R. A. & Wiest, J. R. (1996). Importance of the proline residue to the functional activity and metabolic stability of the nematode FMRFamide-related peptide, KPNFIRFamide (PF4). Peptides (in press).CrossRefGoogle Scholar
Leach, L., Trudgill, D. L. & Gahan, P. B. (1987). Immunocytochemical localisation of neurosecretory amines and peptides in the free-living nematode, Goodeyus ulmi. Histochemical Journal 19, 471–5.CrossRefGoogle ScholarPubMed
Li, C. & Chalfie, M. (1986). FMRFamide-like immunoreactivity in C. elegans. Society for Neuroscience Abstracts 12, 246.Google Scholar
Lingueglia, E., Champigny, G., Lazdunski, M. & Pascal, B. (1995). Cloning of the amiloride sensitive FMRFamide peptide-gated sodium channel. Nature 378, 730–3.CrossRefGoogle ScholarPubMed
Lochrie, M. A., Mendel, J. E., Sternberg, P. W. & Simon, M. I. (1991) Homologous and unique G protein alpha subunits in the nematode Caenorhabditis elegans. Cell Regulation 2, 135–54.CrossRefGoogle ScholarPubMed
Marks, N. J., Johnson, S., Maule, A. G., Halton, D. W., Shaw, C., Geary, T. G., Moore, S. & Thompson, D. P. (1996b). Physiological effects of RFamide peptides on muscle strip preparations of Fasciola hepatica (Trematoda: Digenea). Parasitology (in press).CrossRefGoogle Scholar
Marks, N. J., Shaw, C., Davis, J. P., Maule, A. G., Halton, D. W., Verhaert, P., Geary, T. G. & Thompson, D. P. (1996a). Isolation of AF2 (KHEYLRFamide) from Caenorhabditis elegans: evidence for the presence of more than one FMRFamide-related peptide encoding gene. Biochemical and Biophysical Research Communications 217, 845–51.CrossRefGoogle Scholar
Martin, R. J.. (1980). The effect of γ-aminobutyric acid on the input conductance and membrane potential of Ascaris muscle. British Journal of Pharmacology 71, 99106.CrossRefGoogle ScholarPubMed
Martin, R. J., Sitamze, J. M., Duittoz, A. H. & Wermuth, C. G. (1995). Novel arylaminopyridazine- GABA receptor antagonists examined electrophysiologically in Ascaris suum. European Journal of Pharmacology 267, 919.CrossRefGoogle Scholar
Marx, p. (1995). Getting a grip on G protein function in C. elegans. Science 267, 1596–7.CrossRefGoogle Scholar
Maule, A. G., Geary, T. G., Bowman, J. W., Marks, N. J., Blair, K. L., Halton, D. W., Shaw, C. & Thompson, D. p. (1995b). Inhibitory effects of nematode FMRFamide-related peptides (FaRPs) on musclestrips from Ascaris suum. Invertebrate Neuroscience 1, 255–65.CrossRefGoogle Scholar
Maule, A. G., Geary, T. G., Bowman, J. W., Shaw, C., Halton, D. W. & Thompson, D. P. (1996). The pharmacology of nematode FMRFamide-related peptides. Parasitology Today 12, 351–7.CrossRefGoogle ScholarPubMed
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G. & Thim, L. (1994a). The FMRFamide-like neuropeptide AF2 (Ascaris suum) is present in the free-living nematode, Panagrellus redivivus (Nematoda, Rhabditida). Parasitology 109, 351–6.CrossRefGoogle ScholarPubMed
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G. & Thim, L. (1994b). KSAYMRFamide: A novel FMRFamide-related heptapeptide from the free-living nematode, Panagrellus redivivus, which is myoactive in the parasitic nematode, Ascaris suum. Biochemical and Biophysical Research Communications 200, 973–80.CrossRefGoogle ScholarPubMed
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Thim, L., Kubiak, T. M., Martin, R. A. & Geary, T. G. (1995 a). Isolation and preliminary biological characterization of KPNFIRFamide, a novel FMRFamide-related peptide from the freeliving nematode, Panagrellus redivivus. Peptides 16, 8793.CrossRefGoogle ScholarPubMed
Mendel, J. E., Korswagen, H. C., Liu, K. S., Hajducronin, Y. M., Simon, M. I., Plasterk, R. H. A. & Sternberg, P. W. (1995). Participation of the protein Go in multiple aspects of behaviour in C. elegans. Science 267, 1652–5.CrossRefGoogle ScholarPubMed
Pang, F.-Y., Mason, J., Holden-Dye, L., Franks, C. J., Williams, R. G. & Walker, R. J.. (1995). The effects of the nematode peptide, KHEYLRFamide (AF2), on the somatic musculature of the parasitic nematode Ascaris suum. Parasitology 110, 353–62.CrossRefGoogle ScholarPubMed
Price, D. A. & Greenberg, M. J.. (1977). Structure of a molluscan cardioexcitatory neuropeptide. Science 197, 670–1.CrossRefGoogle ScholarPubMed
Rogers, W. P. (1968). Neurosecretory granules in the infective stage of Haemonchus contortus. Parasitology 58, 657–62.CrossRefGoogle Scholar
Rosoff, M. L., Burglin, T. R. & Li, C. (1992). Alternatively spliced transcripts of the flp-l gene encode distinct FMRFamide-like peptides in Caenorhabditis elegans. Journal of Neuroscience 12, 2356–61.CrossRefGoogle ScholarPubMed
Rosoff, M. L., Doble, K. E., Price, D. A. & Li, C. (1993). The flp-l propeptide is processed into multiple, highly similar FMRFamide-like peptides in Caenorhabditis elegans. Peptides 14, 331–8.CrossRefGoogle ScholarPubMed
Sajid, M. & Isaac, R. E. (1994). Metabolism of AF1 (Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH2) in the nematode, Ascaris suum. Biochemical Society Transactions 22, 293S.CrossRefGoogle ScholarPubMed
Sajid, M. & Isaac, R. E. (1995). Identification and properties of a neuropeptide- degrading endopeptidase (neprilysin) of Ascaris suum muscle. Parasitology 111, 599608.CrossRefGoogle ScholarPubMed
Santama, N., Benjamin, P. R. & Burke, J. F. (1995). Alternative RNA splicing generates diversity of neuropeptide expression in the brain of the snail Lymnaea: In situ analysis of mutually exclusive transcripts of the FMRFamide gene. European Journal of Neuroscience 7, 6576.CrossRefGoogle ScholarPubMed
Schinkmann, K. & Li, c. (1992). Localization of FMRFamide-like peptides in Caenorhabditis elegans. Journal of Comparative Neurology 316, 251–60.CrossRefGoogle ScholarPubMed
Schinkmann, K. & Li, c. (1994). Comparison of two Caenorhabditis genes encoding FMRFamide (Phe-Met-Arg-Phe-NH2)-like peptides. Molecular Brain Research 24, 238–46.CrossRefGoogle ScholarPubMed
Segalat, L., Elkes, D. A. & Kaplan, J. M. (1995). Modulation of serotonin-controlled behaviours by Go in Caenorhabditis elegans. Science 267, 1648–51.CrossRefGoogle ScholarPubMed
Silva, I. F. & Plasterk, R. H. A. (1990). Characterization of a G-protein a subunit from the nematode Caenorhabditis elegans. Journal of Molecular Biology 215, 483–7.CrossRefGoogle Scholar
Sithigorngul, P., Stretton, A. O. W. & Cowden, C. (1990). Neuropeptide diversity in Ascaris: an immunocytochemical study. Journal of Comparative Neurology 294, 362–76.CrossRefGoogle ScholarPubMed
Smart, D. S., Johnston, C. F., Curry, W. J., Shaw, C., Halton, D. W., Fairweather, I. & Buchanan, K. D. (1992). Immunoreactivity to two specific regions of chromogranin A in the nervous system of Ascaris suum. Parasitology Research 78, 329–35.CrossRefGoogle ScholarPubMed
Smart, D. S., Johnston, C. F., Shaw, C., Halton, D. W. & Buchanan, K. D. (1993). Use of specific antisera for the localization and quantitation of leucokinin immunoreactivity in the nematode Acaris suum. Comparative Biochemistry and Physiology 106C, 517–22.Google Scholar
Smart, D. S., Johnston, C. F., Maule, A. G., Halton, D. W., Hrckova, G., Shaw, C. & Buchanan, K. D. (1995). Localization of Diploptera punctata allatostatin-like immunoreactivity in helminths: an immunocytochemical study. Parasitology 110, 8796.CrossRefGoogle ScholarPubMed
Stretton, A. O. W., Cowden, C., Sithigorngul, P. & Davis, R. E. (1991). Neuropeptides in the nematode Ascaris suum. Parasitology 102, S107–16.CrossRefGoogle Scholar
Van Der Voorn, L., Gebbink, M., Plasterk, R. H. A. & Ploegh, H. L. (1990). Characterization of a G-protein β-subunit gene from the nematode Caenorhabditis elegans. Journal of Molecular Biology 213, 1726.CrossRefGoogle Scholar
Walker, R. J.. (1992). Neuroactive peptides with an RFamide or Famide carboxyl terminus. Comparative Biochemistry and Physiology 102C, 213–22.Google ScholarPubMed
Wang, Z.Lane, A. B. & Orchard, I. (1995). Coupling of a single receptor to two different G proteins in the signal transaction of FMRFamide-related peptides. Biochemical and Biophysical Research Communications 212(2), 531–8.CrossRefGoogle Scholar
Warbrick, E. V., Rees, H. H. & Howells, R. E. (1992). Immunocytochemical localisation of a FMRFamidelike peptide in the filarial nematodes Dirofilaria immitis and Brugia pahangi. Parasitology Research 78, 252–6.CrossRefGoogle ScholarPubMed
Wikgren, M. C. & Fagerholm, H. P. (1993). Neuropeptides in sensory structures of nematodes. Acta Biologia Hungarica 44, 133–6.Google ScholarPubMed
Yang, H.-Y. T., Fratta, W., Majane, E. A. & Costa, E. (1985). Isolation, sequencing, synthesis and pharmacological characterization of two brain neuropeptides that modulate the action of morphine. Proceedings of the National Academy of Sciences, USA 82, 7757–61.CrossRefGoogle ScholarPubMed