Carmichael F J, Israel Y
J Pharmacol Exp Ther. 1975 Jun;193(3):824-34.
Using a double label technique to preload rat brain cortex slices with different radioactive neurotransmitters (or precursor choline), we have studied the effects of ethanol on the electrically stimulated release of these transmitters. Ethanol inhibited the release of these transmitters, acetylcholine being the most sensitive and occurring at concentrations compatible with moderate to severe intoxication in the rat (IC50 equals 0.17 M). The order of sensitivity to ethanol was acetylcholine greater than serotonin greater than dopamine greater than norepinephrine greater than glutamate greater gamma-aminobutyric acid. Two higher alcohols and two barbiturates were also shown to have a greater inhibitory effect on the stimulated release of acetylcholine than of norepinephrine. The concentrations of all the drugs tested required for 50% inhibition of release of acetylcholine and norepinephrine correlated well with their lipid solubility when corrected for their molecular volumes. The effect of tetrodotoxin and of ouabain on neurotransmitter release was also studied. A comparison of the effects of these two drugs with those of ethanol suggests that the effect of ethanol is consistent with an inhibition of the action potential by this drug, although a specific effect of ethanol on the excitation-coupling process at the synapse cannot by discarded.
我们采用双标记技术用不同的放射性神经递质（或前体胆碱）预加载大鼠大脑皮层切片，研究了乙醇对这些递质电刺激释放的影响。乙醇抑制了这些递质的释放，其中乙酰胆碱最为敏感，在与大鼠中度至重度中毒相当的浓度下即可出现抑制作用（半数抑制浓度[IC50]等于0.17M）。对乙醇的敏感顺序为：乙酰胆碱＞5-羟色胺＞多巴胺＞去甲肾上腺素＞谷氨酸＞γ-氨基丁酸。另外还显示，两种高级醇和两种巴比妥类药物对乙酰胆碱刺激释放的抑制作用比对去甲肾上腺素的抑制作用更强。经分子体积校正后，50%抑制乙酰胆碱和去甲肾上腺素释放所需的所有受试药物浓度与其脂溶性密切相关。还研究了河豚毒素和哇巴因对神经递质释放的影响。将这两种药物的作用与乙醇的作用进行比较表明，乙醇的作用与该药物对动作电位的抑制作用一致，尽管不能排除乙醇对突触处兴奋-偶联过程的特定作用。
