A pharmacological examination of venom from the Papuan taipan

Crachi, Marcus T; Hammer, Leah W.; Hodgson, Wayne Clarence

doi:10.1016/s0041-0101(99)00114-2

Cited by 30 publications

(27 citation statements)

References 23 publications

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“…The venom from the Papuan taipan has postsynaptic neurotoxic activity (Crachi et al, 1999a) that is neutralized by the prior addition of taipan antivenom (Crachi et al, 1999b). However, in the current study, antivenom added at the t 90 time point failed to reverse the indirect twitches, indicating the presence of a presynaptic neurotoxin(s).…”

Section: Discussioncontrasting

confidence: 73%

“…At the conclusion of the experiment, responses to ACh, CCh, and KCl were obtained as described previously. Time taken to reduce the amplitude of the indirect twitches by 90% (t 90 ) was calculated to provide a quantitative measure of neurotoxicity (Crachi et al, 1999a).…”

Section: Cbcnm Preparationmentioning

confidence: 99%

“…Toxin (11 nM) made up in sodium cacodylate-HCl buffer (0.1 M; pH 6.0) and 4-BPB made up in acetone were added to produce a final concentration of 1.8 mM (Abe et al, 1977;Bell et al, 1998;Crachi et al, 1999a). Vials containing the above-mentioned mixture were incubated for 16 h at 30°C.…”

Section: Pla 2 Inhibition With 4-bromophenacyl Bromidementioning

confidence: 99%

“…Venom from the Papuan taipan displays postsynaptic neurotoxic activity (Crachi et al, 1999a) that is prevented by CSL Taipan antivenom (Crachi et al, 1999b). In the current study, taipan antivenom (5 U/ml) added at t 90 (44 Ϯ 8.2 min) failed to reverse or prevent further inhibition of indirect twitches over a period of 2 h (Fig.…”

Section: Chick Biventer Studies: Whole Venommentioning

confidence: 99%

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Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

Kuruppu

Reeve²,

Banerjee³

et al. 2005

J Pharmacol Exp Ther

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The Papuan taipan (Oxyuranus scutellatus canni) is widely distributed throughout much of Papua New Guinea. Although neurotoxicity is a major symptom of envenomation, no neurotoxins have been isolated from this venom. Using a series of size exclusion chromatography steps, we report the isolation of cannitoxin, a presynaptic neurotoxin (44,848 Da) that represents approximately 16% of the whole venom. The toxin displayed high phospholipase A 2 (PLA 2 ) activity (330 Ϯ 5 mol/ min/mg) and caused concentration-dependent (11-66 nM) inhibition of indirect (0.2 ms; 0.1 Hz; supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation without effecting nicotinic receptor agonists. Prior addition of CSL Taipan antivenom (5 U/ml) or inhibition of phospholipase A 2 activity by incubation with 4-bromophenacyl bromide prevented the inhibition of twitches. Cannitoxin is composed of three different subunits, ␣, ␤, and ␥, with the possibility of two ␤ isomers. However, only the ␣ subunit displayed in vitro neurotoxic activity of its own. Thus, cannitoxin is similar in structure and pharmacology to taipoxin, which has been isolated from the closely related Australian species O. scutellatus scutellatus (coastal taipan).Three species of taipans (genus Oxyuranus) have been identified and are considered to be the world's most venomous snakes (Sutherland and Tibballs, 2001 (Broad et al., 1979). However, t 90 (i.e., time to produce 90% inhibition of indirect twitches) data obtained in the chick biventer cervicis nerve-muscle (CBCNM) preparation indicated that O. scutellatus scutellatus venom is more neurotoxic than that of O. scutellatus canni venom (Crachi et al., 1999b). They also showed that CSL Taipan antivenom (CTPV) was markedly more effective in neutralizing the neurotoxic effects of the Papuan or coastal taipan venoms than that of the inland taipan (Crachi et al., 1999b).Presynaptic neurotoxins act at the motor nerve terminal to either facilitate (e.g., dendrotoxin) or inhibit (e.g., ␤-bungarotoxin, taipoxin, and paradoxin) the release of neurotransmitter. All of the presynaptic inhibitors have phospholipase A 2 (PLA 2 ) activity (Harris, 1991). Taipoxin and paradoxin were isolated from the venoms of O. scutellatus scutellatus (Fohlman et al., 1976) and O. microlepidotus, respectively. Taipoxin is a ternary complex of three subunits, ␣-, ␤-, and ␥-taipoxin, that exists in a stoichiometry of 1:1:1 held together by noncovalent interactions. The ␣ subunit is the only subunit with toxic activity on its own. The ␤ subunit is neutral and exists in two isoforms (i.e., ␤ 1 and ␤ 2 ), which are interchangeable in the complex. The ␥ subunit is the largest of the three subunits, and it seems to be glycosylated (FohlArticle, publication date, and citation information can be found at

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Section: Discussioncontrasting

confidence: 73%

Section: Cbcnm Preparationmentioning

confidence: 99%

Section: Pla 2 Inhibition With 4-bromophenacyl Bromidementioning

confidence: 99%

Section: Chick Biventer Studies: Whole Venommentioning

confidence: 99%

See 2 more Smart Citations

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

Kuruppu

Reeve²,

Banerjee³

et al. 2005

J Pharmacol Exp Ther

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“…For crude V. varius mandibular secretion, a concentration of 1 mg kg À1 was required to cause a drop in blood pressure in an anaesthetised rat ) whilst a decrease in blood pressure was seen at doses above 100 mg/kg for synthesised natriuretic peptide (from V. komodoensis) with 400mg/kg required to induce hypotensive collapse (Fry et al 2009). Conversely, in a similar experiment, 10mg/kg of crude Papuan taipan (Oxyuranus scutellatus canni) venom caused a complete respiratory and cardiovascular collapse (Crachi et al 1999). It is safe to say that lizard "venom" is much more inefficient, and coupled with the inefficient delivery method in these species, is it realistic that they will administer sufficient amounts of toxin in a single bite?…”

Section: Shortcomings Of the Toxicofera Hypothesismentioning

confidence: 99%

A Critique of the Toxicoferan Hypothesis

Hargreaves¹,

Tucker²,

Mulley³

et al. 2015

Evolution of Venomous Animals and Their Toxins

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Historically, venom was believed to have evolved twice independently in squamate reptiles, once in the advanced snakes and once in venomous lizards. The presence of putative toxin proteins in the saliva of species usually regarded as non-venomous, and the expression of venom gene homologs in their salivary glands, led to the hypothesis that venom evolved a single time in reptiles. As the single, early origin of venom is synonymous with the Toxicofera clade (Serpentes, Anguimorpha and Iguania), it will subsequently be referred to as the Toxicofera hypothesis. This hypothesis has proved to be remarkably pervasive for almost a decade, but has until recently never been tested. Here, evidence used in support of the Toxicofera hypothesis is reviewed and critically evaluated. Taking into account both new and old data, it appears that this hypothesis is unsupported, and should be subject to further scrutiny and discussion. Finally, the implications of the rejection of the Toxicofera hypothesis are discussed, with respect to the knowledge of venom evolution in the Reptilia and also the practical implications of this knowledge.

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Phospholipase A₂‐dependent effects of the venom from the new guinean small‐eyed snake Micropechis ikaheka

Kuruppu

Hodgson

2005

Muscle and Nerve

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The New Guinean small-eyed snake (Micropechis ikaheka) is a cause of life-threatening envenoming. Previous studies on M. ikaheka venom have indicated the presence of neurotoxins as well as myotoxins. This study examined the in vitro myotoxic effects of M. ikaheka venom and the efficacy of a polyvalent antivenom in neutralizing these effects. Venom (50 microg/ml) produced a slowly developing contracture and inhibition of direct twitches of the chick biventer cervicis nerve-muscle preparation in the presence of tubocurarine (10 microM). Myotoxicity was confirmed by subsequent histological examination of tissues. This myotoxicity was prevented by the prior addition of polyvalent snake antivenom (30 U/ml). However, the addition of antivenom (30 U/ml) 1 h after venom administration failed to reverse or prevent the further inhibition of direct twitches. In addition, venom (1-10 microg/ml) produced concentration-dependent contractions of the guinea-pig isolated ileum. These effects were dependent on phospholipase A2 (PLA2) activity of the venom as evidenced by the ability of the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB; 1.8 mM) to prevent this activity. This study indicates that M. ikaheka venom causes significant myotoxicity and that polyvalent snake antivenom may be a potential treatment for the myotoxic effects in patients envenomed by this species.

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A pharmacological examination of venom from the Papuan taipan

Cited by 30 publications

References 23 publications

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

A Critique of the Toxicoferan Hypothesis

Phospholipase A₂‐dependent effects of the venom from the new guinean small‐eyed snake Micropechis ikaheka

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A pharmacological examination of venom from the Papuan taipan

Cited by 30 publications

References 23 publications

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

Isolation and Pharmacological Characterization of Cannitoxin, a Presynaptic Neurotoxin from the Venom of the Papuan Taipan (Oxyuranus scutellatus canni)

A Critique of the Toxicoferan Hypothesis

Phospholipase A2‐dependent effects of the venom from the new guinean small‐eyed snake Micropechis ikaheka

Contact Info

Product

Resources

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Phospholipase A₂‐dependent effects of the venom from the new guinean small‐eyed snake Micropechis ikaheka