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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.
Neurotoxicology. 2010 Mar; 31(2):239-43.N

Abstract

Based on murine LD(50) 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 6770Da toxin (i.e. alpha-oxytoxin 1) and a 6781Da toxin (i.e. alpha-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both alpha-oxytoxin 1 (0.3-1 microM) and alpha-scutoxin 1 (0.1-1 microM) 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 alpha-oxytoxin 1 was reversed by washing. Cumulative concentration-response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA(2) of alpha-scutoxin 1 being 44.7-fold higher than alpha-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 alpha-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a 'competitive' mode of action, whereas alpha-scutoxin 1 possesses pseudo-irreversible or non-competitive activity.

Authors+Show Affiliations

Monash Venom Group, Department of Pharmacology, Monash University, Victoria 3800, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20036687

Citation

Kornhauser, Rachelle, et al. "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." Neurotoxicology, vol. 31, no. 2, 2010, pp. 239-43.
Kornhauser R, Hart AJ, Reeve S, et al. 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. Neurotoxicology. 2010;31(2):239-43.
Kornhauser, R., Hart, A. J., Reeve, S., Smith, A. I., Fry, B. G., & Hodgson, W. C. (2010). 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. Neurotoxicology, 31(2), 239-43. https://doi.org/10.1016/j.neuro.2009.12.009
Kornhauser R, et al. 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. Neurotoxicology. 2010;31(2):239-43. PubMed PMID: 20036687.
* Article titles in AMA citation format should be in sentence-case
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 J, AU - Reeve,Shane, AU - Smith,A Ian, AU - Fry,Bryan G, AU - Hodgson,Wayne C, Y1 - 2009/12/29/ PY - 2009/10/26/received PY - 2009/12/18/accepted PY - 2009/12/29/entrez PY - 2009/12/29/pubmed PY - 2010/6/17/medline SP - 239 EP - 43 JF - Neurotoxicology JO - Neurotoxicology VL - 31 IS - 2 N2 - Based on murine LD(50) 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 6770Da toxin (i.e. alpha-oxytoxin 1) and a 6781Da toxin (i.e. alpha-scutoxin 1) were isolated from the venoms of O. s. canni and O. scutellatus, respectively, using reverse-phase high performance liquid chromatography. Both alpha-oxytoxin 1 (0.3-1 microM) and alpha-scutoxin 1 (0.1-1 microM) 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 alpha-oxytoxin 1 was reversed by washing. Cumulative concentration-response curves to CCh were obtained in the presence and absence of the toxins with the subsequently determined pA(2) of alpha-scutoxin 1 being 44.7-fold higher than alpha-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 alpha-oxytoxin 1 is atypical of most snake venom post-synaptic neurotoxins displaying a 'competitive' mode of action, whereas alpha-scutoxin 1 possesses pseudo-irreversible or non-competitive activity. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/20036687/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(09)00281-2 DB - PRIME DP - Unbound Medicine ER -