Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder

• Published in: Biochemical Pharmacology
• Main Authors: Wickramaratna, J. C., Fry, B. G., Loiacono, R. E., Aguilar, M. I., Alewood, P. F., Hodgson, W. C.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Pergamon-Elsevier Science Ltd 2004
• Subjects: Pharmacology & Pharmacy; Acantoxin Iva; Alpha7; Death Adder; Neurotoxin; Nicotinic; Venom; Amino-acid-sequence; Long-chain Neurotoxin; Acetylcholine-receptors; Mouse-brain; Binding-sites; Snake-venoms; Antarcticus; Antagonist; Alpha-7; Subunit; 320305 Medical Biochemistry - Proteins and Peptides; C1; 730104 Nervous system and disorders; Antarc*; antarcticus
• Online Access: https://espace.library.uq.edu.au/view/UQ:73246

The present study describes the isolation of the first neurotoxin (acantoxin IVa) from Acanthophis sp. Seram death adder venom and an examination of its activity at nicotinic acetylcholine receptor (naChR) subtypes. Acantoxin IVa (MW 6815; 0.1-1.0 muM) caused concentration-dependent inhibition of indirect twitches (0.1 Hz, 0.2 ms, supramaximal V) and inhibited contractile responses to exogenous nicotinic agonists in the chick biventer cervicis nerve-muscle, confirming that this toxin is a postsynaptic neurotoxin. Acantoxin IVa (1-10 nM) caused pseudo-irreversible antagonism at skeletal muscle nAChR with an estimated pA(2) Of 8.36 +/- 0.17. Acantoxin IVa was approximately two-fold less potent than the long-chain (Type 11) neurotoxin, alpha-bungarotoxin. With a pK(i) value of 4.48, acantoxin IVa was approximately 25,000 times less potent than a-bungarotoxin at alpha7-type neuronal nAChR. However, in contrast to alpha-bungarotoxin, acantoxin IVa completely inhibited specific [H-3]-methyllycaconitine (MLA) binding in rat hippocampus homogenate. Acantoxin IVa had no activity at ganglionic nAChR, alpha4beta2 subtype neuronal nAChR or cytisine-resistant [H-3]-epibatidine binding sites. While long-chain neurotoxin resistant [H-3]-MLA binding in hippocampus homogenate requires further investigation, we have shown that a short-chain (Type 1) neurotoxin is capable of fully inhibiting specific [H-3]-MLA binding. (C) 2004 Elsevier Inc. All rights reserved.