Bioorganic Study on the Neurotoxic Substances from Platypus (Ornithorhynchus anatinus), an Australian Unique Mammal

Kita Masaki, Ohno Osamu, Yamada Kaoru, Kigoshi Hideo, Uemura Daisuke, Black David StC.

doi:10.24496/tennenyuki.52.0_175

The duck-billed platypus (Ornithorhynchus anatinus) is one of the few venomous Australian mammals. The adult male platypus carries a thorn on each hind leg, and uses this device to inject their competitors with poison. However, the structure and function of their active compounds remais unclear. We found that the crude platypus venom showed potent Ca^<2+> influx in human neuroblastoma (IMR-32) cells. Guided by this bioassay, we identified 11 novel peptides, including a heptapeptide 1, H-His-Asp-His-Pro-Asn-Pro-Arg-OH. 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, respectivel. Heptapeptide 1, which is one of he primary components of the venom fluid(-200ng/μL), induced a significant increase in [Ca^<2+>]_i in IMR-32 cells at 75μM. 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. Heptapeptide 1 also facilitated neurogenic twitch in guinea pig ileum speciments at 30μM (39% contraction relative to 1.7μM histamine response). We have also established that a proteinous venom fraction strongly hydrolyzed Pro-Phe-Arg-MCA and cleaved a human low-molucular-weight kininogen, as with porcine pancreas kallikrein. These results indicated that platypus venom contained tissue kallikrein-like protease(s), and its proteolytic activity might synergistically contribute to toxicity through the specific cleavage of venom constituents.

Bioorganic Study on the Neurotoxic Substances from Platypus (Ornithorhynchus anatinus), an Australian Unique Mammal

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