Wada A, Uezono Y, Arita M, Yanagawa Y, Satake M, Izumi F
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Sep;342(3):323-7. doi: 10.1007/BF00169444.
Conotoxin GIIIA and GIIIB from the marine snail Conus geographus have been reported to inhibit voltage-dependent Na channels in skeletal muscle and postganglionic sympathetic neuron, but have no effect on Na channels in brain, giant axon and heart. In eel electroplax, conotoxins were also shown to share the common binding sites with saxitoxin (see review Gray et al. 1988). In bovine adrenal medullary cells, conotoxin GIIIA inhibited veratridine-induced influx of 22Na, 45Ca and secretion of catecholamines with an IC50 of 6 mumols/l while saxitoxin suppressed veratridine-induced responses with an IC50 of 6.3 nmol/l. [3H]Saxitoxin binding to the cells was inhibited by unlabeled saxitoxin with an IC50 of 5.1 nmol/l, but was slightly reduced by 10 mumols/l conotoxin GIIIA. Conotoxin GIIIA, at 10 mumols/l, did not alter carbachol-induced influx of 22Na, 45CA and secretion of catecholamines as well as high K-induced 45Ca influx and catecholamine secretion. These results indicate that conotoxin GIIIA, at concentrations 950 fold higher than saxitoxin, inhibits Na influx via voltage-dependent Na channels, but has no effect on the nicotinic receptor-ion channel complex or the voltage-dependent Ca channels. Conotoxin GIIIA seems to bind at the sites which are distinct from saxitoxin, but are functionally linked to the voltage-dependent Na channels. Conotoxins may be useful for the classification of Na channels in excitable cell membranes.
据报道，来自地纹芋螺的芋螺毒素GIIIA和GIIIB可抑制骨骼肌和节后交感神经元中电压依赖性钠通道，但对脑、巨轴突和心脏中的钠通道无影响。在电鳗电板中，芋螺毒素也被证明与石房蛤毒素具有共同的结合位点（见Gray等人1988年的综述）。在牛肾上腺髓质细胞中，芋螺毒素GIIIA抑制藜芦定诱导的22Na、45Ca内流以及儿茶酚胺分泌，IC50为6 μmol/l，而石房蛤毒素抑制藜芦定诱导的反应，IC50为6.3 nmol/l。未标记的石房蛤毒素以5.1 nmol/l的IC50抑制[3H]石房蛤毒素与细胞的结合，但10 μmol/l的芋螺毒素GIIIA使其略有降低。10 μmol/l的芋螺毒素GIIIA不会改变卡巴胆碱诱导的22Na、45Ca内流以及儿茶酚胺分泌，也不会改变高钾诱导的45Ca内流和儿茶酚胺分泌。这些结果表明，芋螺毒素GIIIA在浓度比石房蛤毒素高950倍时，通过电压依赖性钠通道抑制钠内流，但对烟碱受体离子通道复合物或电压依赖性钙通道无影响。芋螺毒素GIIIA似乎结合在与石房蛤毒素不同但在功能上与电压依赖性钠通道相关的位点。芋螺毒素可能有助于对可兴奋细胞膜中的钠通道进行分类。
