Ohizumi Y, Minoshima S, Takahashi M, Kajiwara A, Nakamura H, Kobayashi J
J Pharmacol Exp Ther. 1986 Oct;239(1):243-8.
Geographutoxin II (GTX II, 3 X 10(-9) to 10(-7) M) from a cone shell Conus geographus inhibited twitch responses of the isolated mouse diaphragm to direct stimulation in a dose-dependent manner. The contraction of the diaphragm induced by grayanotoxin I or veratridine was abolished by GTX II (3 X 10(-7) M), whereas the contractile response to KCI or caffeine was not affected. GTX II induced similar effects on isolated bullfrog sartorius muscles, but required higher concentrations (6 X 10(-7) to 3 X 10(-6) M). GTX II (greater than 10(-6) M) inhibited or abolished the action potential evoked in sartorius muscles markedly. In the isolated guinea pig vas deferens and ileum, GTX II caused a dose-dependent inhibition of the twitch responses to indirect nerve stimulation at concentrations of 3 X 10(-8) to 10(-6) M and 10(-7) to 10(-6) M, respectively. But the toxin had no effect on the dose contractile-response curves for norepinephrine, carbamylcholine or KCI in the vas deferens and for carbamylcholine or histamine in the ileum. GTX II (5 X 10(-8) to 10(-6) M) decreased norepinephrine release induced by veratridine from the vas deferens in a dose-dependent manner. These results suggest that GTX II blocks the voltage-sensitive Na channels in the cell membrane of skeletal muscles and autonomic nerves and these may play an important role in the mechanism of inhibitory effects of GTX II on contractile responses of these tissues to electrical stimulation.
来自地纹芋螺的地纹芋螺毒素II（GTX II，3×10⁻⁹至10⁻⁷ M）以剂量依赖性方式抑制离体小鼠膈肌对直接刺激的抽搐反应。GTX II（3×10⁻⁷ M）可消除灰藜毒素I或藜芦定诱导的膈肌收缩，而对氯化钾或咖啡因的收缩反应无影响。GTX II对离体牛蛙缝匠肌有类似作用，但所需浓度更高（6×10⁻⁷至3×10⁻⁶ M）。GTX II（大于10⁻⁶ M）可显著抑制或消除缝匠肌中诱发的动作电位。在离体豚鼠输精管和回肠中，GTX II分别在3×10⁻⁸至10⁻⁶ M和10⁻⁷至10⁻⁶ M的浓度下，对间接神经刺激引起的抽搐反应产生剂量依赖性抑制。但该毒素对输精管中去甲肾上腺素、氨甲酰胆碱或氯化钾以及回肠中氨甲酰胆碱或组胺的剂量-收缩反应曲线无影响。GTX II（5×10⁻⁸至10⁻⁶ M）以剂量依赖性方式减少藜芦定诱导的输精管去甲肾上腺素释放。这些结果表明，GTX II可阻断骨骼肌和自主神经细胞膜上的电压敏感性钠通道，这可能在GTX II对这些组织电刺激收缩反应的抑制机制中起重要作用。
