CHARACTERIZATION OF OXYGENATED FATTY ACID METABOLITES BY CAPILLARY GC/MS

有人假设酒精中毒的部分病因可能是 与脂肪酸和前列腺素代谢异常有关， 在发现乙醇的行为效应可以通过 前列腺素合成酶抑制剂预给药。直接证据 对于乙醇诱导的中枢神经系统野牡丹素的变化一直是矛盾的。 因此，我们开发了一种灵敏和特异的检测方法，基于选定的- 离子监测，电子捕获负离子化GC/MS检测 N-甲基甲肟，五氟苄基酯，三甲基硅醚 PGE_2、PGE_1、PGF_（1a）和6-酮-PGF_（1a）的衍生物低于15pg/mL， 健康人和戒酒者的腰椎CSF。为了 为了研究其他测量中枢神经系统胰高血糖素的方法，我们探索了 体内微透析技术和体外组织切片技术。 细胞外液中前列腺素E_2、前列腺素D_（2a）、6-酮-前列腺素F_（1a）和血栓素B_2浓度 使用微透析从大鼠脑中体内取样。的最低水平 所测量的可以代表在所述细胞中二十烷酸类的体内产生的基线。 中枢神经系统，而在最初的高水平存在 采样期被认为是由于急性穿透损伤， 微透析探针非麻醉方法学的扩展 动物可以提供用于测量乙醇的体内效应的有用模型 对中枢神经系统中类花生酸产生的影响。结果在 大鼠额叶皮层的体外组织切片制备，显示没有 在对照和乙醇之间类二十烷酸产生显著差异 暴露的组织，必须合理化与行为研究表明， 显著减弱乙醇对中枢神经系统的影响 在给予类二十烷酸合成抑制剂之后。组织 切片数据表明类花生酸简单酶促刺激 在体外不发生通过乙醇的生产。

it has been hypothesized that part of the etiology of alcoholism may be linked to aberrant fatty acid and prostaglandin metabolism, based primarily upon the finding that behavioral effects of ethanol can be modulated by preadministration of prostaglandin synthetase inhibitors. Direct evidence for ethanol induced changes in CNS prostaglandins has been contradictory. Therefore, we developed a sensitive and specific assay based on selected- ionmonitoring, electron-capture negative ionization GC/MS detection of the N-methyl methoxime, pentafluorobenzyl ester, tris-trimethylsilyl ether derivatives of PGE2, PGE1, PGF1a, and 6-keto-PGF1a were below 15pg/mL in lumbar CSF of healthy humans and abstinent alcoholics. In order to investigate other means of measuring CNS prostaglandins, we explored both in vivo microdialysis techniques and in vitro tissue slice techniques. Extracellular fluid concentrations of PGE2, PGD2a, 6-keto-PGF1a and TXB2 were sampled from rat brain in vivo using microdialysis. The lowest levels measured may represent baseline in vivo production of eicosaniods in the central nervous system, whereas the higher levels present in the initial sampling period were believed to be due to the acute penetration injury of the microdialysis probe. Extension of the methodology o unanesthetized animals may provide a useful model for measuring in vivo effects of ethanol on eicosanoid production in the central nervous system. Results with in vitro tissue slice preparations of rat frontal cortex, showing no significant difference in eicosanoid production between control and ethanol exposed tissues, must be rationalized with behavioral studies showing significant attentuation of thanol's central nervous system effects following administration of eicosanoid synthesis inhibitors. The tissue slice data indicate that a simple enzymatic stimulation of eicosanoid production by ethanol does not occur, in vitro.