Isolation, pharmacology and gene organization of KPSFVRFamide: A neuropeptide from Caenorhabditis elegans

To date, 53 peptides with C-terminal RFamides have been identified by the g enome sequencing project in the nematode, Caenorhabditis elegans. In this s tudy the FMRFamide-related peptide (FaRP) KPSFVRFamide (879.90 Da [MH](+)) was structurally characterized from extracts of the nematode, Caenorhabditi s elegans. Two copies of KPSFVRFamide are encoded by a gene designated flp- 9. RT-PCR identified a single cDNA product which was confirmed as flp-9 by sequence determination. Flp-9 cDNA was isolated from larval stages of C. el egans but was not detected-in adult worms, indicating that its expression i s may be developmentally regulated. KPSFVRFamide displays sequence homology to the nematode peptide, KPNFIRFamide (PF4). The physiological effects of KPSFVRFamide, PF4 and the chimeras, KPNFVRFamide and KPSFIRFamide, were mea sured on body wall muscle and the vagina vera of the parasitic nematode, As caris suum. KPNFVRFamide and KPNFIRFamide had Cl--dependent inhibitory acti vity on innervated and denervated muscle-preparations, whereas KPSFVRFamide and KPSFIRFamide did not elicit a detectable physiological effect. Althoug h all 4 peptides had inhibitory effects on the vagina vera, KPSFVRFamide an d KPSFIRFamide (threshold, greater than or equal to 0.1 mu M) were less pot ent than KPNFVRFamide and KPNFIRFamide (threshold, greater than or equal to 10 nM). (C) 1999 Academic Press.