Abstract
A large number of FMRFamide-related peptides (FaRPs) are found in nematodes, and some of these are known to influence tension and contractility of neuromuscular strips isolated fromAscaris suum body wall. Relaxation of these strips has been noted with five nematode FaRPs. The inhibitory actions of SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2) appear to be mediated by nitric oxide, as previously demonstrated with inhibitors of nitric oxide synthase (NOS). This present study showed that the effects of PF1 were also dependent on external Ca++ and were reduced by the Ca++-channel blocker verapamil, observations consistent wirh the finding that nematode NOS is Ca++-dependent. KSAYMRFamide (PF3), KPNFIRFamide (PF4) and KNAFIRFamide (an alanine substituted analog of KNEFIRFamide, AF1, termed A3AF1) also relaxed A.suum muscle strips, but these responses were not affected by NOS inhibitors. PF3 inhibited the activity of strips prepared from the dorsal side of the worm, but contracted ventral strips. Both effects were dependent on the presence of ventral/dorsal nerve cords (unlike PF1/PF2) and were attenuated in medium which contained high K+ or low Ca++. PF4-induced muscle relaxation and hyperpolarization were independent of nerve cords, but were reversed in Cl-free medium, unlike PF1 or PF3. The PF4 effect physiologically desensitized muscle strips to subsequent treatment with PF4 and/or GABA. However, PF4 and GABA were not synergistic in this preparation. The effects of GABA, but not PF4, were reduced in muscle strips treated with the GABA antagonist, NCS 281-93. Following PF4 (or GABA) relaxation, subsequent treatment with higher doses of PF4 caused muscle strip contraction. A3AF1 was found to relax muscle strips and hyperpolarize muscle cells independently of the ventral and dorsal nerve cords, K+, Ca++, and Cl-, and mimicked the inhibitory phase associated with the exposure of these strips to AF1. On the basis of anatomical and ionic dependence, these data have delineated at least four distinct inhibitory activities attributable to nematode FaRPs. Clearly, a remarkably complex set of inhibitory mechanisms operate in the nematode neuromuscular system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ash, A. S. F. and Tucker, J. F. (1967) The bioassay of γ-aminobutyric acid using a muscle preparation fromAscaris lumbricoides.J. Pharm. Pharmacol.,19, 240–245.
Baldwin, E. and Moyle, V. (1947) An isolated nerve-muscle preparation fromAscaris lumbricoides.J. Exp. Biol.,23, 277–291.
Bascal, Z. A., Montgomery, A., Holden-Dye, L., Williams, R. G., Thorndyke, M. C. and Walker, R. J. (1995) Histochemical mapping of NADPH diaphorase in the nervous system of the parasitic nematodeAscaris suum.Parasitology,110, 625–637.
Bowman, J. W., Geary, T. G. and Thompson, D. P. (1990) Electrophysiological characterization of the effects of nematode FMRFamide-like neuropeptides onAscaris suum muscle cells.Neurotox '90 Absts.,129.
Bowman, J. W., Winterrowd, C. A., Friedman, A. R., Thompson, D. P., Klein, R. D., Davis, J. P., Maule, A. G., Blair, K. L. and Geary, T. G. (1995a) Nitric oxide mediates the inhibitory effects of SDPNFLRFamide, a nematode FMRFamide-like neuropeptide, inAscaris suum.J. Neurophysiol.,74, 1880–1888.
Bowman, J. W., Friedman, A. R., Thompson, D. P., Ichhpurani, A. K., Kellman, M. F., Marks, N. J., Maule, A. G. and Geary, T. G. (1995b) Structure-activity relationships of KNEFIRFamide (AF1), a nematode FMRFamide-related peptide, onAscaris suum muscle.Peptides, in press.
Cottrell, G. A. (1993) The wide range of actions of the FMRFamide-related peptides and the biological importance of second messengers. InComparative Molecular Neurobiology, ed. Y. Pichon, pp. 279–285. Basel, Switzerland: Birkhäuser Verlag.
Cowden, C. and Stretton, A. O. W. (1993) AF2, anAscaris neuropeptide: Isolation, sequence and bioactivity.Peptides,14, 423–430.
Cowden, C. and Stretton, A. O. W. (1995) Eight novel FMRFamide-like neuropeptides isolated from the nematodeAscaris suum.Peptides,16, 491–500.
Cowden, C., Stretton, A. O. W. and Davis, R. E. (1989) AF1, a sequenced bioactive neuropeptide isolated from the nematodeAscaris suum.Neuron,2, 1465–1473.
Davis, R. E. and Stretton, A. O. W. (1989) Passive membrane properties of motorneurons and their role in long-distance signaling in the nematodeAscaris.J. Neurosci.,9, 403–414.
Del Castillo, J., De Mello, W. C. and Morales, T. (1964a) Influence of some ions on the membrane potential ofAscaris muscle.J. Gen. Physiol.,48, 129–140.
Del Castillo, J., De Mello, W. C. and Morales, T. (1964b) Inhibitory action of γ-aminobutyric acid (GABA) onAscaris muscle.Experientia,20, 141–143.
Fields, C. G., Lloyd, D. H., Mcdonald, R. L., Ottetson, K. M. and Nobel, R. L. (1991) HBTU activation for automated Fmoc solid-phase peptide synthesis.Pept. Res.,4, 95–101.
Franks, C. J., Holden-Dye, L., Williams, R. G., Pang, F. Y. and Walker, R. J. (1994) A nematode FMRFamide-like peptide, SDPNFLRFamide (PF1), relaxes the dorsal muscle strip preparation ofAscaris suum.Parasitology,108, 229–236.
Fritz, L. C., Wang, C. C. and Gorio, A. (1979) Avermectin B1a irreversibly blocks postsynaptic potentials at the lobster neuromuscular junction by reducing muscle membrane resistance.Proc. Natl. Acad. Sci. USA,76(4), 2062–2066.
Geary, T. G., Price, D. A., Bowman, J. W., Winterrowd, C. A., Mackenzie, C. D., Garrison, R. D., Williams, J. F. and Friedman, A. R. (1992) Two FMRFamide-like peptides from the nematode,Panagrellus redivivus.Peptides,13, 209–214.
Goldschmidt, R. (1908) Das nervensystem vonAscaris lumbricoides und megalocephala.Z. Wissen. Zool.,90, 73–136.
Halton, D. W., Shaw, C., Maule, A. G. and Smart, D. (1994) Regulatory peptides in helminth parasites.Adv. Parasitol.,34, 163–227.
Kass, I. S., Larsen, D., Wang, C. C. and Stretton, A. O. W. (1982)Ascaris suum: differential effects of avermectin B1a on the intact animal and neuromuscular strip preparations.Exp. Parasitol.,54, 166–174.
Lee, D. L. and Atkinson, H. J. (1977) Neuro-muscular physiology. InPhysiology of nematodes, Second Edition, pp. 133–144. New York: Columbia University Press.
Martin, R. J. (1980) The effect of γ-aminobutyric acid on the input conductance and membrane potential ofAscaris muscle.Br. J. Pharmacol.,71, 99–106.
Martin, R. J. (1993) Neuromuscular transmission in nematode parasites and antinematodal drug action.Pharmacol. Ther.,58, 13–50.
Martin, R. J., Pennington, A. J., Duittoz, A. H., Robertson, S. and Kusel, J. R. (1991) The physiology and pharmacology of neuromuscular transmission in the nematode parasite,Ascaris suum.Parasitology,102, S41-S48.
Martin, R. J., Sitamze, J.-M., Duittoz, A. H. and Wermuth, C. G. (1995) Novel arylaminopyridazine-GABA receptor antagonists examined electrophysiologically inAscaris suum.Eur. J. Pharmacol.,276, 9–19.
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G. and Thim, L. (1994a) KSAYMRFamide: a novel FMRFamide-related heptapeptide from the free-living nematode,Panagrellus redivivus, which is myoactive in the parasitic nematode,Ascaris suum.Biochem. Biophys. Res. Commun.,200(2), 973–980.
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G. and Thim, L. (1994b) The FMRFamide-like neuropeptide AF2 (Ascaris suum) is present in the freeliving nematode,Panagrellus redivivus (Nematoda, Rhabditida).Parasitology,109, 351–356.
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G., Kubiak, T. M., Martin, R. A. and Thim, L. (1995) Isolation and preliminary biological characterization of KPNFIRFamide, a novel FMRFamide-related peptide from the free-living nematode,Panagrellus redivivus.Peptides,16, 87–93.
Mellin, T. N., Busch, R. D. and Wang, C. C. (1983) Postsynaptic inhibition of invertebrate neuromuscular transmission by avermectin B1a.Neuropharmacology,22, 89–96.
Rosoff, M. L., Burglin, T. R. and Li, C. (1992) Alternatively spliced transcripts of theflp-1 gene encode distinct FMRFamide-like peptides inCaenorhabditis elegans.J. Neurosci.,12, 2356–2361.
Rosoff, M. L., Doble, K. E., Price, D. A. and Li, C. (1993) Theflp-1 propeptide is processed into multiple highly similar FMRFamide-like peptides inCaenorhabditis elegans.Peptides,14, 331–338.
Stretton, A. O. W. (1976) Anatomy and development of the somatic musculature of the nematodeAscaris.J. Exp. Biol.,64, 773–788.
Stretton, A. O. W., Cowden, C., Sithigorngul, P. and Davis, R. E. (1991) Neuropeptides in the nematodeAscaris suum.Parasitology,102, S107-S116.
Stretton, A. O. W., Donmoyer, J., Davis, R. E., Meade, J. and Sithigorngul, P. (1992) Motor behavior and motor nervous system function in the nematodeAscaris suum.J. Parasitol.,78(2), 206–214.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maule, A.G., Geary, T.G., Bowman, J.W. et al. Inhibitory effects of nematode FMRFamide-related peptides (FaRPs) on muscle strips fromAscaris suum . Invertebrate Neuroscience 1, 255–265 (1995). https://doi.org/10.1007/BF02211027
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02211027