Changes in locomotory behavior and cAMP produced in Ascaris suum by neuropeptides from Ascaris suum or Caenorhabditis elegans.
Injection of Ascaris FMRFamide-like (AF) peptides and peptides encoded by genes in Caenorhabditis elegans were analyzed for effects on locomotion, body waveforms, and cAMP concentrations in adult female Ascaris suum. Injection of AF1 (KNEFIRFamide) or AF2 (KHEYLRFamide) inhibited the propagation of locomotory waves and reduced the number of waveforms, decreased the body length, and caused a large, long-lasting increase in cAMP. Muscle tissue was identified as a major source of the cAMP response induced by AF1. The AF1 analog AF1R6A did not affect cAMP levels by itself, but inhibited the cAMP response produced by AF1. AF8 (KSAYMRFamide) produced ventral coiling in the behavioral assay, and AF10 (GFGDEMSMPGVLRFamide) decreased the body length and increased the number of body waveforms. In dorsal muscle strips, AF10 produced a long-lasting contraction. Neither AF8 nor AF10 changed cAMP concentrations. AF17 (FDRDFMHFamide) increased body length and decreased cAMP. The neuropeptides encoded by C. elegans genes flp-4, flp-7, flp-9, and flp-13 produced paralysis and loss of waveforms, increased body length and, like AF17, decreased cAMP. Three new predicted peptides from C. elegans genome sequences were synthesized and tested. One produced ventral coiling but no change in cAMP; the other two gave no detectable responses. The fact that C. elegans neuropeptides produce behavioral and physiological effects in A. suum suggests that structurally related peptides may exist in A. suum. The profound changes in cAMP produced by some neuropeptides has important implications for understanding cAMP signaling and shows that neuropeptide-mediated signal transduction pathways are potential targets for anthelmintic drug development.
Reinitz
C A
CA
Department of Zoology, University of Wisconsin-Madison, 1117 West Johnson Street, Madison, WI 53706, USA.
Herfel
H G
HG
Messinger
L A
LA
Stretton
A O
AO
D000818:Animals; D017165:Ascaris suum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000737:chemistry*; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D009068:Movement / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D015398:Signal Transduction
D009479:Neuropeptides; D009842:Oligopeptides; D000242:Cyclic AMP