Duck-Billed Platypus Venom Peptides Induce Ca2+ Influx in Neuroblastoma Cells

The duck-billed platypus (Ornithorhynchus anatinus) is one of the few venomous Australian mammals. We previously found that its crude venom potently induces Ca2+ influx in human neuroblastoma IMR-32 cells. Guided by this bioassay, we identified 11 novel peptides, including the heptapeptide H-His-Asp-His-Pro-Asn-Pro-Arg-OH (1). Compounds 1-4 and 5-11 coincided with the 6-9 N-terminal residues of Ornithorhynchus venom C-type natriuretic peptide (OvCNP) and the 132-150 part of OvCNP precursor peptide, respectively. Heptapeptide 1, which is one of the primary components of the venom fluid (similar to 200 ng/mu L), induced a significant increase in [Ca2+](i) in IMR-32 cells at 75 mu M. To the best of our knowledge, this is the first example of the isolation of the N-terminal linear fragments of CNPs in any mammal.