MODE OF ACTION OF THE ANTHELMINTICS MORANTEL, PYRANTEL AND LEVAMISOLE ON MUSCLE-CELL MEMBRANE OF THE NEMATODE ASCARIS-SUUM
MODE OF ACTION OF THE ANTHELMINTICS MORANTEL, PYRANTEL AND LEVAMISOLE ON MUSCLE-CELL MEMBRANE OF THE NEMATODE ASCARIS-SUUM
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DOI：
10.1002/ps.2780160612
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发表时间：
1985-12-01
期刊：
影响因子：
--
通讯作者：
GRATION, KAF
中科院分区：
文献类型：
--
作者：
HARROW, ID;GRATION, KAF
采用细胞内电流和电压钳技术，研究驱虫药、莫兰酮、吡喃酮和左旋咪唑对猪蛔虫肌细胞袋区的作用方式。驱虫药和O-乙酰胆碱(ACh)的微灌流增加了肌袋的输入电导和去极化肌袋的膜电位。根据剂量-电导关系确定了这些药物的相对效力，发现它们的相对效力为：莫兰特尔=吡喃酮>；左旋咪唑&ACh。大剂量(10微米)的莫兰泰对ACh反应有拮抗作用。在电压钳下(-80~+10 mV)测量ACh诱发电流。在-80 mV至0 mV的膜电位范围内，ACh微灌可产生电压依赖性的内向电流。膜电位在-30~+10 mV范围内呈线性关系。直接测量其反转电位约为+10 mV。当膜电位大于-30 mV时，这种关系变为非线性，且非线性程度依赖于ACh的浓度。莫兰特、吡喃酮和左旋咪唑的电流-电压关系也具有线性(-30~0 mV)和非线性成分。通过外推电流-电压关系的线性分量，每个激动剂的反转电位约为+10 mV，表明ACh和驱虫药激活了相同的阳离子通道。ACh和吡喃酮之间竞争同一膜受体的证据是通过从双管微吸管通过离子电泳法递送每个激动剂而获得的。结果表明，驱虫药、莫兰特、吡喃酮和左旋咪唑对猪链霉菌肌袋膜上的ACh受体具有较强的激动剂作用。
Intracellular current and voltage clamp techniques were used to investigate the mode of action of the anthelmintics, morantel, pyrantel and levamisole applied to the bag region of Ascaris suum muscle cells. Microperfusion of the anthelmintics and of O-acetylcholine (ACh) increased the input conductance and depolarised the membrane potential of the muscle bags. The relative potencies of these drugs were determined from dose-conductance relationships and found to be: morantel = pyrantel > levamisole > ACh. High doses (> 10 .mu.m) of morantel caused antagonism of ACh responses. ACh-induced currents were measured under voltage clamp (over the range -80 to +10 mV). At membrane potentials between -80 and 0mV, microperfusion of ACh induced a voltage-dependent inward current. The current-voltage relationship was linear for membrane potentials in the range -30 to +10 mV. The reversal potential was measured directly and found to be about +10 mV. The relationship became non-linear at membrane potentials more negative than -30 mV, and the degree of non-linearity was dependent upon the concentration of ACh. The current-voltage relationships for morantel, pyrantel and levamisole also possessed both linear (-30 to 0 mV) and non-linear components. The reversal potential for each agonist, determined by extrapolation of the linear component of the current-voltage relationship, was approximately +10 mV, indicating the same cation channels were activated both by ACh and the anthelmintics. Evidence for competition between ACh and pyrantel for the same membrane receptor was obtained using iontophoretic delivery of each agonist from a double-barrelled micropipette. It is concluded that the anthelmintics, morantel, pyrantel and levamisole act as potent agonists at ACh receptors on muscle bag membranes of A. suum.