Action neuromusculaire de trois venins d'Hydrophiidés

Cheymol, J; Barme, M; Bourillet, F; Roch-Arveiller, M

doi:10.1016/0041-0101(67)90162-6

Cited by 21 publications

(17 citation statements)

References 20 publications

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“…haemachatus 9B lacked powerful activity on skeletal muscle cells. This confirms earlier pharmacological [18] and toxicological [27] findings that this molecule is virtually an inactive homologue of the cardiotoxin group.…”

Section: Biological Activitjsupporting

confidence: 79%

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Cobra cardiotoxins

Hodges

Agbaji

Harvey

et al. 1987

European Journal of Biochemistry

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A new preparative method for isolating homogeneous cardiotoxins from cobra venoms is described. The technique, based on reverse-phase high-pressure liquid chromatography, was used to isolate eight cardiotoxins of known sequence from four different venoms. In each case the method was found to be particularly efficient at removing trace quantities of contaminating phospholipase. Cardiotoxins isolated in this manner were found to retain their full biological activity.Without exception the purified cardiotoxins lacked powerful haemolytic activity at concentrations up to 0.01 mM (about 100 pg ml-l), although some lysis of human erythrocytes was induced at higher concentrations. The cardiotoxins displayed a wide range of depolarizing activity on cultured skeletal muscle, the lowest activity being associated with the highest LDS0 value.Correlating variations in amino acid sequence and variations in depolarization potency revealed the importance of residues in the second and third loops, especially lysine-46, serine-48 and lysine-52, together with a number of hydrophobic residues. Further modifications of pharmacological activity were associated with the presence of additional basic residues in the first and second loops and to minor differences in secondary structure.Cardiotoxins are the major toxic proteins found in cobra venoms. They are made up of 60-63 amino acid residues in a single polypeptide chain cross-linked by four disulphide bonds. Over 40 homologous cardiotoxins have been isolated and sequenced [l]. Cardiotoxins produce depolarization of nerve and muscle cells, but their mechanism of action is unclear and the structural features that contribute to activity are unknown [2].One problem that has hindered the elucidation of the mechanism of action of cardiotoxins is that phospholipase Az can coelute with the toxins during ion-exchange chromatography [3]. As the presence of phospholipase A2 greatly enhances the ability of cardiotoxins to lyse erythrocytes [4, 51, contamination with this enzyme complicates studies on the effects of cardiotoxins. Various procedures have been used to render cardiotoxins phospholipase-free, including gel chromatography in the presence of 8 M urea [6], hydrophobic chromatography [4] and immunoaffinity chromatography [7]. However, each method has associated disadvantages.The purpose of our work was threefold: firstly, to establish a convenient method for isolating phospholipase-free cardiotoxins; secondly, to determine the relative effects of a range of cardiotoxins on an electrically excitable and on an inexcitable tissue (skeletal muscle and erythrocytes, respectively); and thirdly, to analyse the structure/activity relationships for the series of cardiotoxins. MATERIALS AND METHODS VenomsCardiotoxins were isolated from the venoms of Nuja naja siamensis, Nuja haje annuli&era, Naja melunoleuca (Sigma Correspondence to R. C. Hider, Department of Chemistry, University of Essex, Wivenhoe Park, Colchester, England C 0 4 3SQ Chemical Co., Poole, UK) and Hemachatus huemachatus (D. Muller,...

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Section: Biological Activitjsupporting

confidence: 79%

“…The elution profiles obtained from both gel permeation and ion-exchange chromatography were similar to previously reported isolations [8,[15][16][17][18]. All the major fractions resulting from ion-exchange chromatography steps were subjected to amino acid analysis.…”

Section: Toxin Isolationsupporting

confidence: 54%

Cobra cardiotoxins

Hodges

Agbaji

Harvey

et al. 1987

European Journal of Biochemistry

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“…The progressive and irreversible nature of E. schistosa venom block was demonstrated in our present experiments and has often been shown previously (Carey & Wright, 1961;Cheymol et al, 1967;Geh, 1968;Geh & Chan, 1973 (Chang & Lee, 1963;Datyner & Gage, 1973a,b). It is not possible at this stage to identify which component(s) or combination of active constituents in the crude E. schistosa venom that can be responsible for the effects seen now and in previous investigations.…”

Section: Discussionsupporting

confidence: 65%

“…Attempts made to elucidate its site of action at the neuromuscular junction have revealed a presynaptic effect with relatively small doses (Geh & Chan, 1973;Toh, Geh & Chan, 1975); however, an action on postjunctional receptors by the crude venom has been suggested (Carey & Wright, 1961;Cheymol et al, 1967;Geh, 1968). Since it is possible for crude snake venoms to have two main sites of action (Chang & Lee, 1963;Datyner & Gage, 1973a,b) the present electrophysiological study was designed to determine whether the action of crude E. schistosa venom is preor postjunctional or even both.…”

Section: Introduction Methodsmentioning

confidence: 99%

“…The crude venom of Enhydrina schistosa, a sea snake found in Malaysian waters, has been shown to paralyse skeletal muscle by blocking transmission across the neuromuscular junction (Carey & Wright, 1961;Cheymol, Barme, Bourillet & Roch-Arveiller, 1967;Geh, 1968). Attempts made to elucidate its site of action at the neuromuscular junction have revealed a presynaptic effect with relatively small doses (Geh & Chan, 1973;Toh, Geh & Chan, 1975); however, an action on postjunctional receptors by the crude venom has been suggested (Carey & Wright, 1961;Cheymol et al, 1967;Geh, 1968).…”

Section: Introduction Methodsmentioning

confidence: 99%

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