INTERACTION OF INSECTICIDES OF THE PYRETHROID FAMILY WITH SPECIFIC BINDING-SITES ON THE VOLTAGE-DEPENDENT SODIUM-CHANNEL FROM MAMMALIAN BRAIN
INTERACTION OF INSECTICIDES OF THE PYRETHROID FAMILY WITH SPECIFIC BINDING-SITES ON THE VOLTAGE-DEPENDENT SODIUM-CHANNEL FROM MAMMALIAN BRAIN
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DOI：
10.1016/0006-8993(88)90284-3
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发表时间：
1988-08-30
期刊：
影响因子：
2.9
通讯作者：
LAZDUNSKI, M
中科院分区：
文献类型：
--
作者：
LOMBET, A;MOURRE, C;LAZDUNSKI, M
通过测量大鼠脑膜中的神经毒素结合和神经母细胞瘤细胞中神经毒素激活的 22Na+ 流入，可以确定拟除虫菊酯和滴滴涕对钠通道的作用位点和机制。一种高效拟除虫菊酯，RU 39568，单独将[3H]蝙蝠毒素A 20-α-苯甲酸盐的结合增强高达30倍。这种效应通过作用于脑膜钠通道蛋白不同位点的神经毒素（例如海葵毒素和短尾藻毒素）的作用而放大。各种拟除虫菊酯和滴滴涕增强箭鲀毒素结合的能力与其激活河鲀毒素敏感的 22Na+ 摄取的能力有关。这些结果表明拟除虫菊酯和滴滴涕作用的变构机制涉及优先结合钠通道的活性状态，钠通道对神经毒素具有高亲和力，导致钠通道持续激活。拟除虫菊酯不会阻断[3]河豚毒素结合、125I-苏卡达海葵毒素2结合、125I-Tityus serrulatus毒素.gamma。分别结合于神经毒素受体位点1、3和4。拟除虫菊酯似乎作用于钠通道上的新神经毒素受体位点。拟除虫菊酯在大鼠脑中的分布通过定量放射自显影程序使用拟除虫菊酯的性质来确定，以揭示[3H]蝙蝠毒素A 20-α-苯甲酸盐的结合位点。
Measurement of neurotoxin binding in rat brain membranes and neurotoxin-activated 22Na+ influx in neuroblastoma cells were used to define the site and mechanism of action of pyrethroids and DDT on sodium channels. A highly potent pyrethroid, RU 39568, alone enhanced the binding of [3H]batrachotoxinin A 20-.alpha.-benzoate up to 30 times. This effect was amplified by the action of neurotoxins such as sea anemone toxins and brevetoxin acting at different sites of the sodium channel protein in brain membranes. The ability of various pyrethroids and DDT to enhance batrachotoxin binding was related to their capacity to activate tetrodotoxin sensitive 22Na+ uptake. These results point to an allosteric mechanism of pyrethroids and DDT action involving preferential binding to active states of sodium channels which have high affinity for neurotoxins, causing persistent activation of sodium channels. Pyrethroids do not block [3]tetrodotoxin binding, 125I-Anemonia sulcata toxin 2 binding, 125I-Tityus serrulatus toxin .gamma. binding at neurotoxin receptor sites 1, 3 and 4 respectively. Pyrethroids appear to act at a new neurotoxin receptor site on the sodium channel. The distribution of pyrethroid binding sites in rat brain was determined by quantitative autoradiographic procedures using the property of pyrethroids to reveal binding sites for [3H]batrachotoxinin A 20-.alpha.-benzoate.