Isolation and pharmacological characterisation of hostoxin-1, a postsynaptic neurotoxin from the venom of the Stephen's banded snake (Hoplocephalus stephensi).
Envenoming by the Stephen's banded snake (Hoplocephalus stephensi) is not usually characterised by neurotoxicity. The present study describes the pharmacological characterisation of hostoxin-1 (MW 6660 Da), the first neurotoxin to be isolated from the venom of the Stephen's banded snake. Hostoxin-1 (0.3-1.0 microM) caused concentration-dependent inhibition of indirect twitches of the chick biventer cervicis nerve-muscle preparation. The neurotoxic activity of hostoxin-1 (0.3 microM) was irreversible by washing, but significantly reversed by the addition of CSL tiger snake antivenom (5 units/ml) added at t90 (i.e. time at which twitches were inhibited by 90%). In addition, hostoxin-1 (0.3 microM) inhibited responses to exogenous acetylcholine and carbachol, but not KCl, indicating a postsynaptic mode of action. Hostoxin-1 (5-30 nM) displayed pseudo-irreversible antagonism at the skeletal muscle nicotinic receptor with a pA2 value of 8.45+/-0.32 (i.e. approximately 100-fold more potent than tubocurarine). H. stephensi venom displayed a high level of PLA2 activity (specific activity 100.1+/-4.4 micromol/min/mg). However, the activity of hostoxin-1 was negligible. Partial N-terminal sequencing of hostoxin-1 indicates that it has high sequence homology with other elapid short-chain neurotoxins.
Tan
Li C
LC
Monash Venom Group, Department of Pharmacology, Monash University, Wellington Road, Victoria 3800, Australia.
Kuruppu
Sanjaya
S
Smith
A Ian
AI
Reeve
Shane
S
Hodgson
Wayne C
WC
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000854:Anoplura / Q000737:chemistry*; D002217:Carbachol / Q000494:pharmacology; D002645:Chickens; D018679:Cholinergic Agonists / Q000494:pharmacology; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000302:isolation & purification / Q000494:pharmacology; D066298:In Vitro Techniques; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000302:isolation & purification* / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D020539:Sequence Analysis, Protein / Q000379:methods; D012910:Snake Venoms / Q000302:isolation & purification* / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors
D018679:Cholinergic Agonists; D004546:Elapid Venoms; D009498:Neurotoxins; D012910:Snake Venoms; C514508:hostoxin-1, Hoplocephalus stephensi; D002217:Carbachol; D010741:Phospholipases A; D054467:Phospholipases A2