APEASPFIRFAMIDE, A NOVEL FMRFAMIDE-RELATED DECAPEPTIDE FROM CAENORHABDITIS-ELEGANS - STRUCTURE AND MYOACTIVITY

To date, 9 FMRF amide-related peptides (FaRPs) have been identified in Caenorhabditis elegans. Eight of these peptides are encoded on the fl p-1 gene. However, AF2 (KHEYLRF amide) which was not co-encoded was th e most abundant FaRP identified in ethanolic extracts. Further radioim munometrical screening of acidified ethanol extracts of C. elegans has revealed the presence of other novel FaRPs, which are not encoded on the flp-l gene. One of these peptides has been isolated by sequential rpHPLC and subjected to Edman degradation analysis and gas-phase seque ncing 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 Ha, 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 preparation s of Ascaris suum with a threshold for activity of 10 nM. The inhibito ry response was not dependent on the presence of nerve cords, indicati ng a post-synaptic site-of-action. The relaxation was Ca++- and Cl--in dependent but was abolished in high-KI medium and could be distinguish ed from those of other inhibitory nematode FaRPs, including PF1 (SDPNF LRFamide)and PF1 (KPNFIRF amide). (C) 1997 Academic Press.