Song J H, Nagata K, Tatebayashi H, Narahashi T
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Brain Res. 1996 Feb 5;708(1-2):29-37. doi: 10.1016/0006-8993(95)01239-7.
Type I and type II pyrethroids and dichlorodiphenyltrichloroethane (DDT) are known to modulate the sodium channel to cause the hyperexcitatory symptoms of poisoning in animals. However, since the degrees to which neuronal sodium channel parameters are altered differ, a question is raised as to whether these insecticides bind to the same site in the sodium channel. Competition patch-clamp experiments were performed using rat dorsal root ganglion neurons which are endowed with tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. D-trans-Tetramethrin, S,S-fenvalerate and p,p'-DDT caused a slowly rising and slowly falling tail current to be developed in tetrodotoxin-sensitive sodium channels. In tetrodotoxin-resistant sodium channels, these insecticides, particularly tetramethrin and fenvalerate, generated a large and prolonged tail current upon repolarization. The effects of tetramethrin were reversible after washing with drug-free solution, whereas the effects of fenvalerate and DDT were irreversible. When fenvalerate application was followed by tetramethrin application, the characteristic changes in current by fenvalerate disappeared and the characteristic changes by tetramethrin appeared. After washout, the characteristic current pattern of fenvalerate reappeared. These results can be explained by assuming that the tetramethrin molecule displaces the fenvalerate molecule from the same binding site in the sodium channel protein, or that tetramethrin and fenvalerate bind to separate sodium channel sites which interact allosterically with each other. DDT interacted with fenvalerate and tetramethrin in the same manner.
已知 I 型和 II 型拟除虫菊酯以及二氯二苯三氯乙烷（DDT）可调节钠通道，导致动物中毒时出现过度兴奋症状。然而，由于神经元钠通道参数的改变程度不同，因此提出了一个问题，即这些杀虫剂是否结合在钠通道的同一部位。使用具有对河豚毒素敏感和河豚毒素抗性钠通道的大鼠背根神经节神经元进行了竞争膜片钳实验。右旋反式氯菊酯、S,S-氰戊菊酯和 p,p'-DDT 在对河豚毒素敏感的钠通道中引起缓慢上升和缓慢下降的尾电流。在对河豚毒素抗性的钠通道中，这些杀虫剂，特别是氯菊酯和氰戊菊酯，在复极化时产生大而持久的尾电流。用无药物溶液冲洗后，氯菊酯的作用是可逆的，而氰戊菊酯和 DDT 的作用是不可逆的。当先应用氰戊菊酯再应用氯菊酯时，氰戊菊酯引起的电流特征变化消失，氯菊酯引起的特征变化出现。洗脱后，氰戊菊酯的特征电流模式重新出现。这些结果可以通过假设氯菊酯分子从钠通道蛋白的同一结合位点取代氰戊菊酯分子，或者氯菊酯和氰戊菊酯结合到彼此变构相互作用的不同钠通道位点来解释。DDT 与氰戊菊酯和氯菊酯的相互作用方式相同。
