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 mu M) caused concentration-dependent inhibition of indirect twitches of the chick biventer cervicis nerve-muscle preparation. The neurotoxic activity of hostoxin-1 (0.3 mu M) was irreversible by washing, but significantly reversed by the addition of CSL tiger snake antivenom (5 units/ml) added at t(90) (i.e. time at which twitches were inhibited by 90%). In addition, hostoxin-1 (0.3 mu M) 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 pA(2) value of 8.45 +/- 0.32 (i.e. approximately 100-fold more potent than tubocurarine). H. stephensi venom displayed a high level of PLA(2) activity (specific activity 100.1 +/- 4.4 mu mol/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. (c) 2006 Elsevier Ltd. All rights reserved.