Nomura T, Nishizaki T
Department of Physiology, Kobe University School of Medicine, Japan.
Neurosci Lett. 1997 Dec 19;239(2-3):73-6. doi: 10.1016/s0304-3940(97)00911-7.
Although the cholinergic system is proposed to be involved in methamphetamine (MeAMPH)-induced abnormal behaviors, no direct evidence has been provided yet. The present study investigated the effects of MeAMPH on acetylcholine (ACh)-evoked currents in the neuronal nicotinic ACh receptors (alpha7) expressed in Xenopus oocytes. MeAMPH enhanced the currents in a time- and dose-dependent manner at concentrations ranged from 1 nM to 3 microM, reaching a maximum of 150% 30 min after treatment. Lesser potentiation was observed at higher concentrations (>3 microM) and instead, the currents were inhibited at more than 10 microM MeAMPH with a slow reverse after washing-out of the drug. The current potentiation or depression was caused via a pathway independent of G-protein, protein kinase C or cAMP-dependent protein kinase. The ACh dose-response curve was shifted to the left and to the right after treatment with 1 and 100 microM MeAMPH, respectively, suggesting that MeAMPH potentiated or inhibited ACh-evoked currents by a change in the affinity for ACh. The actions of MeAMPH on the neuronal nicotinic ACh receptors may represent a cellular mechanism for MeAMPH-induced abnormal behaviors and sensitization.
尽管有观点认为胆碱能系统参与甲基苯丙胺（MeAMPH）诱发的异常行为，但尚未有直接证据。本研究调查了MeAMPH对非洲爪蟾卵母细胞中表达的神经元烟碱型乙酰胆碱受体（α7）上乙酰胆碱（ACh）诱发电流的影响。在1 nM至3 μM的浓度范围内，MeAMPH以时间和剂量依赖的方式增强电流，处理后30分钟达到最大值的150%。在较高浓度（>3 μM）下观察到较小的增强作用，相反，在超过10 μM的MeAMPH作用下电流受到抑制，药物洗脱后有缓慢的恢复。电流的增强或抑制是通过一条独立于G蛋白、蛋白激酶C或环磷酸腺苷依赖性蛋白激酶的途径引起的。分别用1 μM和100 μM的MeAMPH处理后，ACh剂量反应曲线向左和向右移动，表明MeAMPH通过改变对ACh的亲和力来增强或抑制ACh诱发的电流。MeAMPH对神经元烟碱型乙酰胆碱受体的作用可能代表了MeAMPH诱发异常行为和敏感化的细胞机制。
