Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneurons.
Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneurons.
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DOI：
10.1085/jgp.101.2.271
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发表时间：
1993-02
期刊：
影响因子：
--
通讯作者：
Stretton AO
中科院分区：
文献类型：
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作者：
Segerberg MA;Stretton AO
胆碱能激动剂乙酰胆碱（ACh）、尼古丁和毛果芸香碱可使猪蛔虫的肌肉去极化和收缩。 100 microM d-管箭毒碱 (dTC)（一种烟碱拮抗剂）可将 ACh 的剂量依赖性去极化和收缩抑制约两个数量级，但 100 microM N-甲基东莨菪碱 (NMS)（一种毒蕈碱拮抗剂）仅抑制约五倍。 NMS 本身可以使正常和突触分离的肌肉细胞去极化。 NMS 或 dTC 均不能始终拮抗毛果芸香碱的肌肉去极化作用。在 DE1、DE2、DI 和 VI 类运动神经元上检测到 ACh 受体，因为 ACh 诱导输入阻力降低。这些输入电阻的变化可以通过用无药盐水冲洗或使用 dTC 来逆转。单独应用 NMS 可以降低 DE1 运动神经元的输入电阻，但不能降低 DE2、DI 或 VI 运动神经元的输入电阻。与 ACh 的作用相反，DE1 中 NMS 的作用不会被 dTC 逆转，这表明 NMS 敏感位点可能不会对 ACh 做出反应。 dTC 拮抗通过向 DE1 和 DE2 运动神经元注射去极化电流而引起的肌肉兴奋性突触反应；然而，NMS 仅拮抗 DE1 和 DE3 类运动神经元的突触输出，这种效应更可能是由运动神经元传导衰竭而不是受体的药物阻断产生的。产生肌肉极化和收缩、乙酰胆碱拮抗、输入阻力降低和突触拮抗这些变化所需的 NMS 浓度为 100 µM，或者比幼虫蛔虫匀浆和成年秀丽隐杆线虫中 [3H]NMS 的结合亲和力高出五个数量级以上（Segerberg，M. A. 1989。博士论文。大学）威斯康星-麦迪逊，麦迪逊，威斯康星州）。这些结果描述了烟碱样药理学，但肌肉和运动神经元对毒蕈碱剂也有不寻常的反应。
The cholinergic agonists acetylcholine (ACh), nicotine, and pilocarpine produced depolarizations and contractions of muscle of the nematode Ascaris suum. Dose-dependent depolarization and contraction by ACh were suppressed by about two orders of magnitude by 100 microM d- tubocurarine (dTC), a nicotinic antagonist, but only about fivefold by 100 microM N-methyl-scopolamine (NMS), a muscarinic antagonist. NMS itself depolarized both normal and synaptically isolated muscle cells. The muscle depolarizing action of pilocarpine was not consistently antagonized by either NMS or dTC. ACh receptors were detected on motorneuron classes DE1, DE2, DI, and VI as ACh-induced reductions in input resistance. These input resistance changes were reversed by washing in drug-free saline or by application of dTC. NMS applied alone lowered input resistance in DE1, but not in DE2, DI, or VI motorneurons. In contrast to the effect of ACh, the action of NMS in DE1 was not reversed by dTC, suggesting that NMS-sensitive sites may not respond to ACh. Excitatory synaptic responses in muscle evoked by depolarizing current injections into DE1 and DE2 motorneurons were antagonized by dTC; however, NMS antagonized the synaptic output of only the DE1 and DE3 classes of motorneurons, an effect that was more likely to have been produced by motorneuron conduction failure than by pharmacological blockade of receptor. The concentration of NMS required to produce these changes in muscle polarization and contraction, ACh antagonism, input resistance reduction, and synaptic antagonism was 100 microM, or more than five orders of magnitude higher than the binding affinity for [3H]NMS in larval Ascaris homogenates and adult Caenorhabditis elegans (Segerberg, M. A. 1989. Ph.D. thesis. University of Wisconsin-Madison, Madison, WI). These results describe a nicotinic- like pharmacology, but muscle and motorneurons also have unusual responses to muscarinic agents.