Tieman T L, Steel D J, Gor Y, Kehoe J, Schwartz J H, Feinmark S J
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Neurophysiol. 2001 May;85(5):2150-8. doi: 10.1152/jn.2001.85.5.2150.
Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by alpha-conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. These currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance and the activation of 8-lipoxygenase have similar pharmacological profiles. Both are stimulated by suberyldicholine and nicotine, and both are inhibited by alpha-bungarotoxin. Like the sustained chloride conductance, the activation of 8-lipoxygenase is not blocked by alpha-conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor sufficient for the formation of the lipid metabolites. In addition, the application of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis.
乙酰胆碱（ACh）可激活海兔神经元中的两种氯离子电导，这两种电导可通过其动力学和药理学特性加以区分。一种是快速脱敏电流，可被α-芋螺毒素ImI阻断，另一种是持续电流，对该毒素不敏感。这些电流在海兔神经元中呈差异表达。我们在此报告，对ACh产生持续氯离子电导反应的神经元也会生成8-脂氧合酶代谢产物。持续氯离子电导和8-脂氧合酶的激活具有相似的药理学特征。二者均受辛二酰胆碱和尼古丁刺激，且均被α-银环蛇毒素抑制。与持续氯离子电导一样，8-脂氧合酶的激活也不会被α-芋螺毒素ImI阻断。尽管代谢反应和电生理反应之间存在相似性，但8-脂氧合酶代谢产物的生成似乎并不依赖于离子电流，因为氯离子内流对于脂质代谢产物的形成既非必要条件也非充分条件。此外，百日咳毒素的应用阻断了ACh激活的花生四烯酸释放及随后8-脂氧合酶代谢产物的产生，然而ACh诱导的氯离子电导激活并不依赖于G蛋白。我们的结果与以下观点一致，即激活持续氯离子电导的烟碱型ACh受体可独立于氯离子内流启动脂质信使合成。
