INTERACTION OF ETHANOL AND MEMBRANE ETHER LIPIDS

这项建议将解决乙醇损伤和细胞之间的关系， 膜醚脂质，主要是缩醛磷脂。 最初的方法将 将膜醚脂质浓度和组成与 酒精暴露 该组合物将以总乙醇计制成。 剂量和暴露时间。 乙醇诱导膜的意义 醚脂质修饰最初将通过以下相关性进行评估： 具有身体依赖性和/或耐受性的浓度和组合物 乙醇 细胞膜中的醚脂替代物 含量可能代表对乙醇刺激的适应性，将通过以下方法进行评价： 测定缩醛磷脂浓度对物理性质的影响 （粘度、相变和相分离） 脂质体，以及从处理的脂质体中分离的膜级分， 动物 膜型缩醛磷脂的功能意义也将在 通过观察到缩醛磷脂 可以操纵鱼中枢神经系统膜的浓度， 环境温度的变化。 因此，缩醛磷脂浓度可以 不依赖于完整生物体中的慢性乙醇暴露而改变。 对急性乙醇的行为反应可以独立测量 既往乙醇暴露，并分析血浆酶原 浓度和组成。 调查的第二阶段将 阐明代谢途径中的机制或特定反应 酒精暴露的影响。 合成或 将估计降解为乙醇引起的血浆酶原变化 用（1- 14 C）十六醇（1- 14 C）乙酸酯和14 C-乙醇胺标记 在存在或不存在乙醇的情况下的缩醛磷脂。 三种不同 化合物还可以预测特定的 在合成途径中被抑制或刺激的反应 乙醇 最初的实验将使用神经母细胞瘤进行 细胞保持在培养物中。 如果在此过程中发现特定病变， 系统中，将使用大鼠CNS组织评价反应。

This proposal will address the relationship between ethanol insult and cell membrane ether lipids, primarily plasmalogens. The initial approach will be to correlate membrane ether lipid concentration and composition with ethanol exposure. The composition will be made in terms of total ethanol dose and period of exposure. The significance of ethanol induced membrane ether lipid modification will be assessed initially by correlation of concentration and composition with physical depenence and/or tolerance to ethanol. The possibility that alternatives in cell membrane ether lipid content may represent adaptation to ethanol insult will be evaluated by measuring the effect of plasmalogen concentration on physical properties (viscosity, phase transition and phase separation) of multilamellar liposomes, as well as well membrane fractions isolated from treated animals. The functional significance of membrane plasmalogens will also be evaluated by taking advantage of the observation that plasmalogen concentrations of fish central nervous system membranes can be manipulated by change in environment temperature. Thus, plasmalogen concentration can be altered independent of chronic ethanol exposure in an intact organism. The behavioral response to acute ethanol can then be measured independent of prior ethanol exposure and analyzed in regard to plasmalogen concentration and composition. The second phase of this investigation will address the mechanism or specific reaction in the metabolic pathway influenced by ethanol exposure. Relative contribution of synthesis or degradation to ethanol elicited changes in plasmalogen will be estimated using (1-14C) hexadecanol (1-14C) acetate and 14C-ethanolamine to label plasmalogen in the presence or absence of ethanol. The three different compounds would also allow prediction to be made concerning specific reaction(s) in the synthetic pathway which are inhibited or stimulated by ethanol. The initial experiments will be carried out using neuroblastoma cells maintained in culture. If specific lesions are identified in this system the reactions will be appraised using rat CNS tissue.