ETHANOL STIMULATED TAURINE RELEASE FROM ASTROGLIA

乙醇中毒的基本机制是 没有被很好地理解。 许多使用完整动物的研究可能会混淆 中枢神经系统的极端复杂性。 使用均质的研究 细胞群大大降低了这种复杂性。 我们研究了 使用培养的星形胶质细胞的乙醇的影响。 这些研究 表明乙醇刺激牛磺酸释放的方式类似于 β-肾上腺素能激动剂血清素和κ-鸦片剂U-50488 乙醇刺激释放具有剂量依赖性。 浓度为0.075% 乙醇刺激50%的牛磺酸释放， 肾上腺素能激动剂异丙肾上腺素的浓度。 因此，在本发明中， 与中毒相关的乙醇浓度可能会影响牛磺酸 在剂量-反应曲线的动态部分， 浓度的变化对释放有很大的影响。 乙醇，就像 异丙肾上腺素和5-羟色胺刺激蛋白质磷酸化。 几种蛋白质的磷酸化可以在时间上与 牛磺酸释放。 这些蛋白质的磷酸化在 加入乙醇，3分钟时最强烈， 类似地，牛磺酸释放在3分钟时最大，并且在30分钟时显著降低。 与异丙肾上腺素不同，乙醇不刺激增加 在细胞内浓度的腺苷3 '，5'一磷酸（cAMP）。 因此，乙醇一定是通过一种 cAMP独立机制。 这些结果表明，乙醇 刺激牛磺酸的释放， 表明星形胶质细胞可以作为研究 与乙醇相关的急性效应的细胞机制 中毒

The basic underlying mechanisms responsible for ethanol intoxication are not well understood. Many studies using intact animals may be confounded by the extreme complexity of the CNS. Studies using homogeneous populations of cells greatly reduce this complexity. We have studied the effects of ethanol using astroglial cells in culture. These studies indicate that ethanol stimulates taurine release in a manner similar to beta-adrenergic agonists, serotonin, and the kappa-opiate, U-50,488. Ethanol-stimulated release is dose-dependent. A concentration of 0.075% ethanol stimulates 50% as much taurine release as a maximally effective concentration of the beta-adrenergic agonist isoproterenol. Thus, concentrations of ethanol associated with intoxication may affect taurine release in the dynamic portion of the dose-response curve where small changes in concentration have large effects on release. Ethanol, like isoproterenol and serotonin, stimulates protein phosphorylation. Phosphorylation of several proteins can be temporally correlated with taurine release. Phosphorylation of these proteins is undetectable before addition of ethanol and is most intense by 3 min, and declines greatly by 30 min. Similarly taurine release is maximal at 3 min and is much reduced after 30 min. Unlike isoproterenol, ethanol does not stimulate increases in intracellular concentrations of adenosine 3',5' monophosphate (cAMP). Thus, ethanol must be affecting protein phosphorylation by a cAMP-independent mechanism. These results demonstrate that ethanol stimulates taurine release at pharmacologically significant doses and indicate that astroglial cells may serve as an excellent model for studying cellular mechanisms underlying acute effects associated with ethanol intoxication.