Jones L S, Lapadula D M, Lewis D V, Abou-Donia M B
Department of Anatomy, University of South Carolina, School of Medicine, Columbia 29208.
Mol Chem Neuropathol. 1990 Aug-Oct;13(1-2):1-16. doi: 10.1007/BF03159904.
Diisopropyl phosphorofluoridate (DFP), an insecticide, is a potent anticholinesterase that binds essentially irreversibly to acetylcholinesterase, resulting in severe, acute neurologic pathology, and less severe, but longer-lasting, delayed neuropathy. We report here on the short-term effects of bath-applied DFP on extracellularly recorded responses from CA3 and CA1 of rat hippocampus. Exposure to 10 microM DFP evokes low amplitude, spontaneous bursts in CA3 generally within 10 minutes, and the bursting does not reverse with washing. The CA1 neuronal population usually bursts synchronously with CA3, but the population events are of low amplitude and sometimes not detectable, implying a differential sensitivity to DFP. These effects were partially blocked by the muscarinic antagonist atropine, while the cholinergic antagonist gallamine had little effect. Also, the reversible anticholinesterase physostigmine could, within temporal limits, protect slices from DFP's effects, implicating the cholinergic system as the probable mediator in the first stages of DFP-induced epileptogenesis.
二异丙基氟磷酸酯（DFP）是一种杀虫剂，是一种强效抗胆碱酯酶，它与乙酰胆碱酯酶的结合基本不可逆，会导致严重的急性神经病理学变化以及不太严重但持续时间更长的迟发性神经病变。我们在此报告了浴用DFP对大鼠海马体CA3和CA1区细胞外记录反应的短期影响。暴露于10微摩尔的DFP通常在10分钟内会在CA3区引发低幅度的自发爆发，且这种爆发不会因冲洗而逆转。CA1神经元群体通常与CA3同步爆发，但群体事件幅度较低，有时无法检测到，这意味着对DFP的敏感性存在差异。这些效应被毒蕈碱拮抗剂阿托品部分阻断，而胆碱能拮抗剂加拉明几乎没有作用。此外，可逆性抗胆碱酯酶毒扁豆碱在一定时间范围内可以保护切片免受DFP的影响，这表明胆碱能系统可能是DFP诱导癫痫发生初期的介导因素。
