A novel D-amino acid-containing peptide, fulyal, coexists with fulicin gene-related peptides in Achatina atria.

ABSTRACT

Fulicin (Phe-D-Asn-Glu-Phe-Val-NH2) is a neuropeptide from ganglia of the African giant snail (Achatina fulica). Previously, the sequences of nine fulicin gene-related peptides (FGRP-1 to -9) have been predicted from the cDNA encoding the ganglia fulicin precursor and the transcripts have been detectable in the heart. We synthesized twenty peptides related to fulicin and FGRPs containing either an L- or a D-amino acid at position 2 and used them to identify FGRPs in atrial extracts. We identified ten alpha-amidated peptides, including fulicin and confirmed their structures as follows Tyr-Ala-Glu-Phe-Leu-NH2 (FGRP-9), [D-Ala2]FGRP-9 (fulyal), [L-Asn2]fulicin, fulicin, Ser-Tyr-Asp-Phe-Val-NH2 (FGRP-2), Thr-Tyr-Asp-Phe-Leu-NH2 (FGRP-3), Tyr-Asp-Phe-Ile-NH2 (FGRP-5), Ser-Pro-Tyr-Asp-Phe-Ile-NH2 (FGRP-6), Asn-Tyr-Asp-Phe-Val-NH2 (FGRP-7) and Ser-Pro-Tyr-Asp-Phe-Val-NH2 (FGRP-8). We analyzed the biological activities of synthetic FGRPs using the snail penis retractor muscle. The results revealed that fulyal remarkably potentiated the tetanic contraction at concentrations as low as 10(-12) M. FGRP-9 was about 10,000-fold less potent. Fulyal, like fulicin, seems to undergo preferential maturation to participate in the penis retractor muscle contraction as a neuropeptide containing a D-amino acid.