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NEUROPHARMACOLOGY

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

Monash Venom Group, Department of Pharmacology, Monash University, Victoria, Australia (S.K., W.C.H.); Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia (S.R., A.I.S.); and Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore (Y.B., R.M.K.)

The Papuan taipan (Oxyuranus scutellatus canni) is widely distributed throughout much of Papua New Guinea. Although neurotoxicity is a major symptom of envenomation, no neurotoxins have been isolated from this venom. Using a series of size exclusion chromatography steps, we report the isolation of cannitoxin, a presynaptic neurotoxin (44,848 Da) that represents approximately 16% of the whole venom. The toxin displayed high phospholipase A₂ (PLA₂) activity (330 ± 5 µmol/min/mg) and caused concentration-dependent (11–66 nM) inhibition of indirect (0.2 ms; 0.1 Hz; supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation without effecting nicotinic receptor agonists. Prior addition of CSL Taipan antivenom (5 U/ml) or inhibition of phospholipase A₂ activity by incubation with 4-bromophenacyl bromide prevented the inhibition of twitches. Cannitoxin is composed of three different subunits, , , and , with the possibility of two isomers. However, only the subunit displayed in vitro neurotoxic activity of its own. Thus, cannitoxin is similar in structure and pharmacology to taipoxin, which has been isolated from the closely related Australian species O. scutellatus scutellatus (coastal taipan).

Address correspondence to: Dr. Wayne C. Hodgson. Monash Venom Group, Department of Pharmacology, Monash University, Victoria 3800, Australia. E-mail: wayne.hodgson{at}med.monash.edu.au