Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder
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 in...
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2004
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ftunivqespace:oai:espace.library.uq.edu.au:UQ:73246 2023-05-15T13:47:20+02:00 Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder Wickramaratna, J. C. Fry, B. G. Loiacono, R. E. Aguilar, M. I. Alewood, P. F. Hodgson, W. C. 2004-01-01 https://espace.library.uq.edu.au/view/UQ:73246 eng eng Pergamon-Elsevier Science Ltd doi:10.1016/j.bcp.2004.03.033 issn:0006-2952 orcid:0000-0001-6661-1283 orcid:0000-0001-7454-6522 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 Journal Article 2004 ftunivqespace https://doi.org/10.1016/j.bcp.2004.03.033 2020-08-04T02:39:42Z 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. Article in Journal/Newspaper Antarc* antarcticus The University of Queensland: UQ eSpace Biochemical Pharmacology 68 2 383 394 |
institution |
Open Polar |
collection |
The University of Queensland: UQ eSpace |
op_collection_id |
ftunivqespace |
language |
English |
topic |
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 |
spellingShingle |
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 Wickramaratna, J. C. Fry, B. G. Loiacono, R. E. Aguilar, M. I. Alewood, P. F. Hodgson, W. C. Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
topic_facet |
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 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Wickramaratna, J. C. Fry, B. G. Loiacono, R. E. Aguilar, M. I. Alewood, P. F. Hodgson, W. C. |
author_facet |
Wickramaratna, J. C. Fry, B. G. Loiacono, R. E. Aguilar, M. I. Alewood, P. F. Hodgson, W. C. |
author_sort |
Wickramaratna, J. C. |
title |
Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
title_short |
Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
title_full |
Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
title_fullStr |
Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
title_full_unstemmed |
Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder |
title_sort |
isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the acanthophis sp seram death adder |
publisher |
Pergamon-Elsevier Science Ltd |
publishDate |
2004 |
url |
https://espace.library.uq.edu.au/view/UQ:73246 |
genre |
Antarc* antarcticus |
genre_facet |
Antarc* antarcticus |
op_relation |
doi:10.1016/j.bcp.2004.03.033 issn:0006-2952 orcid:0000-0001-6661-1283 orcid:0000-0001-7454-6522 |
op_doi |
https://doi.org/10.1016/j.bcp.2004.03.033 |
container_title |
Biochemical Pharmacology |
container_volume |
68 |
container_issue |
2 |
container_start_page |
383 |
op_container_end_page |
394 |
_version_ |
1766246937608060928 |