Isolation and pharmacological characterization of cannitoxin, a presynaptic neurotoxin from the venom of the Papuan Taipan (Oxyuranus scutellatus canni).
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 micromol/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, alpha, beta, and gamma, with the possibility of two beta isomers. However, only the alpha 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).
Kuruppu
Sanjaya
S
Monash Venom Group, Department of Pharmacology, Monash University, Victoria, Australia.
Reeve
Shane
S
Banerjee
Yajnavalka
Y
Kini
R Manjunatha
RM
Smith
A Ian
AI
Hodgson
Wayne C
WC
D000098:Acetophenones / Q000494:pharmacology; D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D017815:Elapidae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009476:Neurons, Efferent / Q000187:drug effects*; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D010219:Papua New Guinea; D010741:Phospholipases A / Q000032:analysis; D054467:Phospholipases A2; D021122:Protein Subunits / Q000737:chemistry / Q000633:toxicity; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D000098:Acetophenones; D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D021122:Protein Subunits; C507233:cannitoxin, Oxyuranus scutellatus canni; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide