Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Neurosci Res. 2010 Dec;68(4):276-84. doi: 10.1016/j.neures.2010.08.008. Epub 2010 Sep 8.
The actions of paraoxon, an organophosphorus cholinesterase (ChE) inhibitor, on central synaptic transmission and somatic excitability, and the inhibitory effects of atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, and pralidoxime (PAM), an oxime, on these actions were investigated. From rat hippocampal slices, CA1-population spikes (PSs) and CA1-field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were recorded using a multi-electrode array (MEA) system. Statistics were performed using ANOVA with Bonferroni/Dunn testing (n=6 in all data). Paraoxon (1μM) depressed fEPSPs but did not significantly influence PSs. The fEPSP depression was inhibited by pre-, simultaneous and post-treatments with atropine (10μM, p<0.01) and pre-treatment with PAM (10μM, p<0.01). The insignificance of the paraoxon-induced PS change was not altered by pre-, simultaneous and post-treatments with atropine or by pre- and post-treatments with PAM; however, PSs were significantly depressed by simultaneous treatment with paraoxon and PAM (p<0.01). Paraoxon-induced ChE inhibition depresses excitatory synaptic transmission and facilitates somatic excitability mediated by mAChRs, and the latter counteracts influence of the depressed synaptic transmission on somatic action potentials. Atropine and PAM prevent and depress the actions of paraoxon and are more effective with earlier treatment.
对氧磷作为一种有机磷乙酰胆碱酯酶（ChE）抑制剂，其对中枢突触传递和体发性兴奋性的作用，以及阿托品（一种非选择性毒蕈碱乙酰胆碱受体（mAChR）拮抗剂）和氯解磷定（PAM，一种肟）对这些作用的抑制作用，进行了研究。从大鼠海马切片中，使用多电极阵列（MEA）系统记录 CA1 群体峰电位（PS）和 CA1 场兴奋性突触后电位（fEPSP）在 0.1Hz 下的情况。统计学分析采用方差分析和 Bonferroni/Dunn 检验（所有数据 n=6）。对氧磷（1μM）抑制 fEPSP，但对 PS 无明显影响。阿托品（10μM，p<0.01）的预、同时和后处理，以及 PAM（10μM，p<0.01）的预处理均可抑制 fEPSP 抑制。阿托品的预、同时和后处理，以及 PAM 的预和后处理，都不会改变对氧磷引起的 PS 变化的无显著性；然而，PS 会被同时用对氧磷和 PAM 处理显著抑制（p<0.01）。对氧磷诱导的 ChE 抑制会抑制兴奋性突触传递，并促进由 mAChRs 介导的体发性兴奋性，后者会抵消抑制性突触传递对躯体动作电位的影响。阿托品和 PAM 可预防和抑制对氧磷的作用，并且早期处理更有效。
