Variations in the pharmacological profile of post-synaptic neurotoxins isolated from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal (Oxyuranus scutellatus scutellatus) taipans

Rachelle Kornhauser, Andrew James Hart, Shane Bernadine Reeve, Alexander Ian Smith, Bryan G Fry, Wayne Clarence Hodgson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Based on murine LD50 values, the taipans (i.e. Oxyuranus microlepidotus, Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous snake genus in the world. Despite this, little is known about the toxins contained in their venoms. The aim of the present study was to isolate and characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O. s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology. A 6770 Da toxin (i.e. a-oxytoxin 1) and a 6781 Da toxin (i.e. a-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both a-oxytoxin 1 (0.3a??1 mM) and a-scutoxin 1 (0.1a??1 mM) caused concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Contractile responses to exogenous carbachol (CCh), but not potassium chloride (KCl), were inhibited by both toxins, suggesting a post-synaptic mode of action. The inhibitory effect of a-oxytoxin 1 was reversed by washing. Cumulative concentrationa?? response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA2 of a-scutoxin 1 being 44.7-fold higher than a-oxytoxin 1 (i.e. 8.38 - 0.59 versus 7.62 - 0.04). The current study shows that Papuan taipan and coastal taipan venom both contain potent post-synaptic neurotoxins which exhibit different pharmacological profiles. The effect of a-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a a??competitivea?? mode of action, whereas a-scutoxin 1 possesses pseudo-irreversible or non-competitive activity.
Original languageEnglish
Pages (from-to)239 - 243
Number of pages5
JournalNeuroToxicology
Volume31
Issue number2
DOIs
Publication statusPublished - 2010

Cite this

@article{64cb3be627024416a8e8d99718d8b041,
title = "Variations in the pharmacological profile of post-synaptic neurotoxins isolated from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal (Oxyuranus scutellatus scutellatus) taipans",
abstract = "Based on murine LD50 values, the taipans (i.e. Oxyuranus microlepidotus, Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous snake genus in the world. Despite this, little is known about the toxins contained in their venoms. The aim of the present study was to isolate and characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O. s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology. A 6770 Da toxin (i.e. a-oxytoxin 1) and a 6781 Da toxin (i.e. a-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both a-oxytoxin 1 (0.3a??1 mM) and a-scutoxin 1 (0.1a??1 mM) caused concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Contractile responses to exogenous carbachol (CCh), but not potassium chloride (KCl), were inhibited by both toxins, suggesting a post-synaptic mode of action. The inhibitory effect of a-oxytoxin 1 was reversed by washing. Cumulative concentrationa?? response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA2 of a-scutoxin 1 being 44.7-fold higher than a-oxytoxin 1 (i.e. 8.38 - 0.59 versus 7.62 - 0.04). The current study shows that Papuan taipan and coastal taipan venom both contain potent post-synaptic neurotoxins which exhibit different pharmacological profiles. The effect of a-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a a??competitivea?? mode of action, whereas a-scutoxin 1 possesses pseudo-irreversible or non-competitive activity.",
author = "Rachelle Kornhauser and Hart, {Andrew James} and Reeve, {Shane Bernadine} and Smith, {Alexander Ian} and Fry, {Bryan G} and Hodgson, {Wayne Clarence}",
year = "2010",
doi = "10.1016/j.neuro.2009.12.009",
language = "English",
volume = "31",
pages = "239 -- 243",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",
number = "2",

}

Variations in the pharmacological profile of post-synaptic neurotoxins isolated from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal (Oxyuranus scutellatus scutellatus) taipans. / Kornhauser, Rachelle; Hart, Andrew James; Reeve, Shane Bernadine; Smith, Alexander Ian; Fry, Bryan G; Hodgson, Wayne Clarence.

In: NeuroToxicology, Vol. 31, No. 2, 2010, p. 239 - 243.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Variations in the pharmacological profile of post-synaptic neurotoxins isolated from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal (Oxyuranus scutellatus scutellatus) taipans

AU - Kornhauser, Rachelle

AU - Hart, Andrew James

AU - Reeve, Shane Bernadine

AU - Smith, Alexander Ian

AU - Fry, Bryan G

AU - Hodgson, Wayne Clarence

PY - 2010

Y1 - 2010

N2 - Based on murine LD50 values, the taipans (i.e. Oxyuranus microlepidotus, Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous snake genus in the world. Despite this, little is known about the toxins contained in their venoms. The aim of the present study was to isolate and characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O. s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology. A 6770 Da toxin (i.e. a-oxytoxin 1) and a 6781 Da toxin (i.e. a-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both a-oxytoxin 1 (0.3a??1 mM) and a-scutoxin 1 (0.1a??1 mM) caused concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Contractile responses to exogenous carbachol (CCh), but not potassium chloride (KCl), were inhibited by both toxins, suggesting a post-synaptic mode of action. The inhibitory effect of a-oxytoxin 1 was reversed by washing. Cumulative concentrationa?? response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA2 of a-scutoxin 1 being 44.7-fold higher than a-oxytoxin 1 (i.e. 8.38 - 0.59 versus 7.62 - 0.04). The current study shows that Papuan taipan and coastal taipan venom both contain potent post-synaptic neurotoxins which exhibit different pharmacological profiles. The effect of a-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a a??competitivea?? mode of action, whereas a-scutoxin 1 possesses pseudo-irreversible or non-competitive activity.

AB - Based on murine LD50 values, the taipans (i.e. Oxyuranus microlepidotus, Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous snake genus in the world. Despite this, little is known about the toxins contained in their venoms. The aim of the present study was to isolate and characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O. s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology. A 6770 Da toxin (i.e. a-oxytoxin 1) and a 6781 Da toxin (i.e. a-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both a-oxytoxin 1 (0.3a??1 mM) and a-scutoxin 1 (0.1a??1 mM) caused concentration-dependent inhibition of indirect twitches in the chick biventer cervicis nerve-muscle preparation. Contractile responses to exogenous carbachol (CCh), but not potassium chloride (KCl), were inhibited by both toxins, suggesting a post-synaptic mode of action. The inhibitory effect of a-oxytoxin 1 was reversed by washing. Cumulative concentrationa?? response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA2 of a-scutoxin 1 being 44.7-fold higher than a-oxytoxin 1 (i.e. 8.38 - 0.59 versus 7.62 - 0.04). The current study shows that Papuan taipan and coastal taipan venom both contain potent post-synaptic neurotoxins which exhibit different pharmacological profiles. The effect of a-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a a??competitivea?? mode of action, whereas a-scutoxin 1 possesses pseudo-irreversible or non-competitive activity.

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