Guppy L J, Littleton J M
Department of Pharmacology & Therapeutics, University of British Columbia, Vancouver, Canada.
Alcohol Alcohol. 1994 May;29(3):283-93.
Male Sprague-Dawley rats were made physically dependent on ethanol by exposure to ethanol vapour in inhalation chambers for 6-10 days. Animals were sacrificed immediately after removal from the chambers. After sacrifice, membrane preparations from cerebral cortex, heart, vas deferens and thigh skeletal muscle were prepared and studied to determine the characteristics of [3H]-nitrendipine binding. In membranes from cerebral cortex, the number of binding sites (Bmax) was increased 40% in preparations from ethanol-dependent rats compared to controls. Similar results were obtained in heart (Bmax increased 125%), vas deferens (Bmax increased 50%) and skeletal muscle (Bmax increased 33%). Binding affinity (Kd) in all these tissues was unchanged. Membranes from cortex and heart were studied more extensively. Displacement studies using other dihydropyridines and the effects of ionic composition on [3H]-nitrendipine binding provided no evidence to suppose that the binding sites induced by the development of ethanol dependence were from a population different from those in control tissues. The results suggest a generalised 'up-regulation' of the dihydropyridine-sensitive subclass of voltage operated calcium channels in excitable tissues from ethanol-dependent rats.
将雄性斯普拉格-道利大鼠置于吸入舱中暴露于乙醇蒸气6至10天，使其对乙醇产生身体依赖。动物从舱中取出后立即处死。处死后，制备大脑皮层、心脏、输精管和大腿骨骼肌的膜制剂并进行研究，以确定[3H]-尼群地平结合的特性。在大脑皮层的膜中，与对照组相比，乙醇依赖大鼠制剂中的结合位点数量（Bmax）增加了40%。在心脏（Bmax增加125%）、输精管（Bmax增加50%）和骨骼肌（Bmax增加33%）中也获得了类似结果。所有这些组织中的结合亲和力（Kd）均未改变。对大脑皮层和心脏的膜进行了更广泛的研究。使用其他二氢吡啶的置换研究以及离子组成对[3H]-尼群地平结合的影响，均未提供证据表明乙醇依赖发展所诱导的结合位点与对照组织中的结合位点来自不同群体。结果表明，乙醇依赖大鼠可兴奋组织中电压门控钙通道的二氢吡啶敏感亚类普遍出现“上调”。
