Background
ω-Conotoxin GVIA is a cone snail toxin that selectively blocks N-type channels in neurons [1].
ω-Conotoxin GVIA binds to human neocortical, rat hippocampal, and chick brain synaptic plasma membranes (IC50s = 4.6, 60, and 150 pM, respectively, in radioligand binding assays) [3,4,5].
ω-Conotoxin GVIA markedly reduced the amplitude of the tetanic contractions of the tibialis anterior muscle in mice, but tetanic facilitation was not impaired. The muscle contractions elicited by direct electrical stimulation were not significantly modified by ω-Conotoxin GVIA. ω-Conotoxin GVIA did not had any significant changes in systemic blood pressure [5].
参考文献:
[1]. H.D. Mansvelder, J.C. Stoof, K.S. Kits. Dihydropyridine block of ω-agatoxin IVA- and ω-conotoxin GVIA-sensitive Ca2+ channels in rat pituitary melanotropic cells.Eur. J. Pharmacol., 311 (1996), pp. 293-304
[2]. Feuerstein, T.J., Dooley, D.J., and Seeger, W. Inhibition of norepinephrine and acetylcholine release from human neocortex by ω-conotoxin GVIA. J. Pharmacol. Exp. Ther. 252(2), 778-785 (1990).
[3]. Lampe, R.A., Lo, M.M., Keith, R.A., et al. Effects of site-specific acetylation on ω-conotoxin GVIA binding and function. Biochemistry 32(13), 3255-3260 (1993).
[4]. Sato, K., Park, N.G., Kohno, T., et al. Role of basic residues for the binding of ω-conotoxin GVIA to N-type calcium channels. Biochem. Biophys. Res. Commun. 194(3), 1292-1296 (1993).
[5]: Rossoni G, Berti F, La Maestra L, Clementi F. ω-Conotoxin GVIA binds to and blocks rat neuromuscular junction. Neuroscience Letters. 1994;176:185-188.
ω-芋螺毒素 GVIA 是一种锥形蜗牛毒素，可选择性地阻断神经元中的 N 型通道[1]。
ω-芋螺毒素 GVIA 与人类新皮质、大鼠海马和鸡脑突触质膜结合（在放射性配体结合试验中，IC50 分别 = 4.6、60 和 150 pM）[3,4,5].
ω-芋螺毒素 GVIA 显着降低了小鼠胫骨前肌的强直收缩幅度，但强直易化作用并未受损。 ω-芋螺毒素 GVIA 未显着改变由直接电刺激引起的肌肉收缩。 ω-芋螺毒素 GVIA 对体循环血压无明显影响[5]。
Protocol
| Cell experiment [1]: |
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Cell lines
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Rat pituitary melanotropic cells
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Preparation Method
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Reaction Conditions
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1 or 10 μM
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Applications
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1 μM ω-Conotoxin GVIA blocked the high voltage-activated current by 25.5±3.6%. The block at 10μM ω-Conotoxin GVIA was 22.9±2.5% (not significantly different from the block by 1μM;n = 3), indicating thatω-Conotoxin GVIA yields a saturating effect.
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| Animal experiment [2]: |
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Animal models
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male COBS CD (SD) rats
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Preparation Method
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In these animals the intravenous administration of graded doses of ω-Conotoxin GVIA (1--2 nmol/kg)
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Dosage form
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Intravenous injection, 1--2 nmol/kg
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Applications
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Intravenous injection caused a progressive loss of tension development of tibialis muscle indirectly evoked by the electrical stimulation of the sciatic nerve, ω-Conotoxin GVIA (1 nmol/kg i.v.) reduced the strength of muscle contraction by 75% in about 27 min (from
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参考文献:
[1]: H.D. Mansvelder, J.C. Stoof, K.S. Kits. Dihydropyridine block of ω-agatoxin IVA- and ω-conotoxin GVIA-sensitive Ca2+ channels in rat pituitary melanotropic cells.Eur. J. Pharmacol., 311 (1996), pp. 293-304
[2]: Rossoni G, Berti F, La Maestra L, Clementi F. ω-Conotoxin GVIA binds to and blocks rat neuromuscular junction. Neuroscience Letters. 1994;176:185-188.
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