Forman S A, Righi D L, Miller K W
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA.
Biochim Biophys Acta. 1989 Dec 11;987(1):95-103. doi: 10.1016/0005-2736(89)90459-8.
The presence of ethanol increases the apparent affinity with which acetylcholine and carbamylcholine elicit 86Rb+ flux from Torpedo nicotinic acetylcholine receptor-rich vesicles at 4 degrees C. Affinity increased exponentially with ethanol concentration, reaching nearly 200-fold by 3.0 M ethanol without sign of saturation. At submaximal agonist concentrations 50-100 mM ethanol enhanced flux by 15-35%, but the maximum agonist-induced flux was unaffected in quenched-flow assays. The effect was independent of the agonist and of the time over which flux was measured (5 ms to 10 s), indicating that ethanol acts before agonist-induced desensitization occurs. Ethanol also caused an increase in the apparent affinity with which acetylcholine caused fast desensitization. This affinity increase was equal to that for flux-response curves, but the maximum fast desensitization rate was increased 50% at 0.5 M ethanol. This was the most pronounced of ethanol's actions and has not been reported before. Prolonged preincubation with 1.0 M ethanol alone reduced agonist-induced flux activity by only 25%. The rate of agonist-induced slow desensitization was also increased, but neither of these effects was as marked as those on fast desensitization and cation flux.
乙醇的存在增加了乙酰胆碱和氨甲酰胆碱在4℃时从富含电鳐烟碱型乙酰胆碱受体的囊泡中引发86Rb+通量的表观亲和力。亲和力随乙醇浓度呈指数增加，在3.0 M乙醇时达到近200倍，且无饱和迹象。在亚最大激动剂浓度下，50 - 100 mM乙醇使通量增加15 - 35%，但在淬灭流测定中最大激动剂诱导的通量不受影响。该效应与激动剂以及测量通量的时间（5毫秒至10秒）无关，表明乙醇在激动剂诱导的脱敏发生之前起作用。乙醇还使乙酰胆碱引起快速脱敏的表观亲和力增加。这种亲和力的增加与通量 - 反应曲线的增加相同，但在0.5 M乙醇时最大快速脱敏速率增加了50%。这是乙醇最显著的作用，之前尚未见报道。单独用1.0 M乙醇长时间预孵育仅使激动剂诱导的通量活性降低25%。激动剂诱导的缓慢脱敏速率也增加了，但这些效应均不如对快速脱敏和阳离子通量的影响明显。
