APEASPFIRFamide, a novel FMRFamide-related decapeptide from Caenorhabditis elegans: structure and myoactivity.
To date, 9 FMRFamide-related peptides (FaRPs) have been identified in Caenorhabditis elegans. Eight of these peptides are encoded on the flp-1 gene. However, AF2 (KHEYLRFamide) which was not co-encoded was the most abundant FaRP identified in ethanolic extracts. Further radioimmunometrical screening of acidified ethanol extracts of C. elegans has revealed the presence of other novel FaRPs, which are not encoded on the flp-1 gene. One of these peptides has been isolated by sequential rpHPLC and subjected to Edman degradation analysis and gas-phase sequencing and the unequivocal primary structure of the decapeptide Ala-Pro-Glu-Ala-Ser-Pro-Phe-Ile-Arg-Phe-NH2 was determined following a single gas-phase sequencing run. The molecular mass of the peptide was found to be 1133.7 Da, determined using a time-of-flight mass spectrometer. Synthetic replicates of this peptide were found to induce a profound relaxation of both dorsal and ventral somatic muscle-strip preparations of Ascaris suum with a threshold for activity of 10 nM. The inhibitory response was not dependent on the presence of nerve cords, indicating a post-synaptic site-of-action. The relaxation was Ca(+2)- and Cl(-)-independent but was abolished in high-K+ medium and could be distinguished from those of other inhibitory nematode FaRPs, including PF1 (SDPNFLRFamide) and PF4 (KPNFIRFamide).
Marks
N J
NJ
Comparative Neuroendocrinology Research Group, Queen's University of Belfast, Northern Ireland.
Maule
A G
AG
Geary
T G
TG
Thompson
D P
DP
Davis
J P
JP
Halton
D W
DW
Verhaert
P
P
Shaw
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001200:Ascaris; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000235:genetics; D019835:FMRFamide; D005796:Genes; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009479:Neuropeptides; D009842:Oligopeptides; C105097:alanyl-prolyl-glutamyl-alanyl-seryl-prolyl-phenylalanyl-isoleucyl-arginyl-phenylalaninamine; D019835:FMRFamide