title: Isolation and pharmacological characterisation of hostoxin-1, a postsynaptic neurotoxin from the venom of the Stephen's banded snake (Hoplocephalus stephensi).
abstract: 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.
authors.affiliation: Monash Venom Group, Department of Pharmacology, Monash University, Wellington Road, Victoria 3800, Australia.
authors.forename: Li C
authors.initials: LC
authors.lastname: Tan
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Kuruppu
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Shane
authors.initials: S
authors.lastname: Reeve
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
mesh_terms: 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
chemical_list: D018679:Cholinergic Agonists; D004546:Elapid Venoms; D009498:Neurotoxins; D012910:Snake Venoms; C514508:hostoxin-1, Hoplocephalus stephensi; D002217:Carbachol; D010741:Phospholipases A; D054467:Phospholipases A2