Toluene-induced alterations in rat synaptosomal membrane composition and function.
Toluene-induced alterations in rat synaptosomal membrane composition and function.
复制标题
甲苯诱导大鼠突触体膜组成和功能的改变。
DOI：
10.1002/jbt.2570030406
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Schatz,RA
中科院分区：
文献类型：
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作者：
LeBel,CP;Schatz,RA
甲苯是一种广泛使用的有机溶剂，可产生急性中枢神经系统（CNS）效应。由于甲苯在CNS中达到相对高的浓度，并且具有极高的亲脂性，因此我们研究了其对大鼠脑膜组成和功能的影响。甲苯（1 g/kg，1 h）未改变总脑微粒体磷脂（PL）或胆固醇（CL）含量。然而，突触体PL减少（24%），而突触体CL不变。PL/CL比，膜流动性的间接指数，没有改变，表明甲苯没有影响膜流动性。采用1，6-二苯基-1，3，5-己三烯（DPH）的荧光偏振研究表明，甲苯在体内（1 g/kg）或体外（0.5 - 5.0 mM）给药后未改变突触体膜流动性。剂量反应和时间过程研究表明，甲苯在1 g/kg，1 h后最大程度地降低突触体PL。剂量反应和时程研究还表明，甲苯诱导的PL降低是磷脂酰乙醇胺（PE）特异性降低的结果。由于PE减少，我们通过研究磷脂甲基化（一种使用PE作为其初始底物的反应）来评估甲苯是否改变了突触体膜功能。当[3 H]-甲硫氨酸用作甲基供体时，甲苯减少甲基基团掺入脂质中，但当[3 H]-腺苷甲硫氨酸用作甲基供体时，甲苯不影响甲基化。这些数据表明，甲苯诱导的突触体PE特异性降低和磷脂甲基化抑制可能改变正常突触功能，并在甲苯CNS效应的作用机制中发挥关键作用。
Toluene is a widely used organic solvent that can produce acute central nervous system (CNS) effects. Since toluene reaches relatively high concentrations in the CNS and is extremely lipophilic, we investigated its effects on rat brain membrane composition and function. Toluene (1 g/kg, lh) did not alter total brain microsomal phospholipid (PL) or cholesterol (CL) content. However, synaptosomal PL was decreased (24%), while synaptosomal CL was unaltered. The PL/CL ratio, an indirect index of membrane fluidity, did not change, suggesting that toluene did not affect membrane fluidity. Fluorescence polarization studies employing 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) showed that toluene did not alter synaptosomal membrane fluidity after administration in vivo (1 g/kg) or in vitro (0.5 to 5.0 mM). Dose‐response and time‐course studies showed that toluene maximally decreased synaptosomal PL after 1 g/kg, 1 h. The dose‐response and time‐course studies also showed that the toluene‐induced decreases in PL were a result of specific decreases in phosphatidylethanolamine (PE). Since PE was decreased, we assessed whether toluene altered synaptosomal membrane function by investigating phospholipid methylation, a reaction which uses PE as its initial substrate. Toluene decreased the incorporation of methyl groups into lipid when [3H]‐methionine was used as the methyl donor, but did not affect methylation when [3H]‐adenosylmethionine was the methyl donor. These data suggest that toluene‐induced specific decreases in synaptosomal PE and inhibition of phospholipid methylation may alter normal synaptic function and play a critical role in the mechanism(s) of action of toluene's CNS effects.