Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom

Belo, Cháriston André Dal; Leite, Gildo Bernardo; Toyama, Marcos H.; Marangoni, Sérgio; Corrado, A.P.; Fontana, Márcio; Southan, Andy; Rowan, Edward G.; Hyslop, Stephen; Rodrigues‐Simioni, Léa

doi:10.1016/j.toxicon.2005.07.016

Cited by 37 publications

(34 citation statements)

References 32 publications

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“…Further evidence for a presynaptic involvement was the marked increase in quantal content within five minutes after the extract addition to the preparations. Dal Belo et al [11] observed a similar increase in the quantal content of PND preparations after ten-minute incubation with MiDCA1, a toxin isolated from coral snake ( Micrurus dumerilli carinicauda ) venom, and concluded that a presynaptic action was involved.…”

Section: Resultsmentioning

confidence: 86%

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Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Rostelato‐Ferreira

Belo

Leite

et al. 2014

J Venom Anim Toxins incl Trop Dis

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BackgroundRhinella schneideri, previously known as Bufo paracnemis, is a common toad in many regions of Brazil. Its venom exerts important cardiovascular effects on humans and other animals. Although this toad venom has been the subject of intense investigations, little is known about its neuromuscular activity.MethodsThe neurotoxicity of a methanolic extract of R. schneideri venom was tested on mouse phrenic nerve-diaphragm (PND) preparations mounted for conventional twitch tension recording – in response to indirect stimulation – and for electrophysiological measurements.ResultsVenom extract (50 μg/mL) increased the muscle twitch tension in PND preparations but did not significantly alter the resting membrane potential values. Electrophysiological evaluations showed that the extract (50 μg/mL) significantly augmented the frequency of miniature end-plate potential (from 38 ± 3.5 to 88 ± 15 after 60 minutes; n = 5; p < 0.05) and quantal content (from 128 ± 13 to 272 ± 34 after five minutes; n = 5; p < 0.05). Pretreatment with ouabain (1 μg/mL) for five minutes prevented the increase in quantal content (117 ± 18 and 154 ± 33 after five and 60 minutes, respectively).ConclusionThese results indicate that the methanolic extract of R. schneideri venom acts primarily presynaptically to enhance neurotransmitter release in mouse phrenic-diaphragm preparations.

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Section: Resultsmentioning

confidence: 86%

“…The quantal content (QC) was estimated as the quotient between the squared average of the EPPs and the variance of the EPPs (indirect method), as described by Dal Belo et al [11]. …”

Section: Methodsmentioning

confidence: 99%

Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Rostelato‐Ferreira

Belo

Leite

et al. 2014

J Venom Anim Toxins incl Trop Dis

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“…In the Americas, the snakes known as coral snakes or corals are those belonging to the genus Leptomicrurus, Micrurus and Micruroides, which are representatives of the Elapidae family in this part of the world (Urdaneta et al, 2004;Dal Belo et al, 2005). This genus presents a greater variability of species in the areas surrounding the equator (Salazar et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2

Terra

Moreira-Dill

Simões-Silva

et al. 2015

Toxicon

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The Micrurus genus is the American representative of Elapidae family. Micrurus spixii is endemic of South America and northern states of Brazil. Elapidic venoms contain neurotoxins that promote curare-mimetic neuromuscular blockage. In this study, biochemical and functional characterizations of M. spixii crude venom were performed and a new neurotoxic phospholipase A2 called MsPLA2-I was isolated. M. spixii crude venom caused severe swelling in the legs of tested mice and significant release of creatine kinase (CK) showing its myotoxic activity. Leishmanicidal activity against Leishmania amazonensis (IC50 1.24 μg/mL) was also observed, along with antiplasmodial activity against Plasmodium falciparum, which are unprecedented for Micrurus venoms. MsPLA2-I with a Mr 12,809.4 Da was isolated from the crude venom of M. spixii. The N-terminal sequencing of a fragment of 60 amino acids showed 80% similarity with another PLA2 from Micrurus altirostris. This toxin and the crude venom showed phospholipase activity. In a mouse phrenic nerve-diaphragm preparation, M. spixii venom and MsPLA2-I induced the blockage of both direct and indirect twitches. While the venom presented a pronounced myotoxic activity, MsPLA2-I expressed a summation of neurotoxic activity. The results of this study make M. spixii crude venom promising compounds in the exploration of molecules with microbicidal potential.

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“…Figure 3A shows a representative record of the neuromuscular blockade caused by a venom concentration of 10 µg/mL and contracture responses to ACh and KCl before and after venom treatment. The decrease of the twitch tension in avian neuromuscular preparations caused by Elapidic venoms has been previously shown [13,21,22,23,24,25]. At these preparations, the muscle-type nicotinic receptors are distributed alongside the muscle fiber characterizing the multiple neuromuscular junctions [26].…”

Section: Resultsmentioning

confidence: 99%

Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae) Venom in Vitro

Carbajal-Saucedo

Floriano

Belo

et al. 2014

Toxins

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In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake) venom (MLV) in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL) neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05). In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL) promoted a slight increase in the amplitude of twitch-tension (3 µg/mL), followed by neuromuscular blockade (n = 4); the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min), without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL) induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs)/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal) to 28 ± 2.5 (t15) and 12 ± 2 (t60)). The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL) was also significantly less negative with MLV (10 µg/mL). Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

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Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom

Cited by 37 publications

References 32 publications

Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Presynaptic neuromuscular action of a methanolic extract from the venom of Rhinella schneideri toad

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2

Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae) Venom in Vitro

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