Woodward J J, Machu T, Leslie S W
Division of Pharmacology, University of Texas, Austin 78712.
Alcohol. 1990 Jul-Aug;7(4):279-84. doi: 10.1016/0741-8329(90)90082-n.
Two groups of adult Sprague-Dawley rats were maintained on a nutritionally complete liquid diet. In one group, 37% of the calories normally provided by dextrin were replaced with ethanol. Animals were maintained on this diet for eight weeks. The addition of ethanol (200 mM) in vitro significantly inhibited both calcium influx and dopamine release from control synaptosomes but did not alter calcium influx or dopamine release from synaptosomes isolated from ethanol-treated rats. The dihydropyridine calcium channel agonist Bay K 8644 (1 nM) significantly increased both calcium entry and dopamine release from control synaptosomes depolarized with 15 mM KCl. Bay K 8644 (1 nM) had no significant effect on either calcium entry or dopamine release in synaptosomes isolated from ethanol-treated animals. This loss of functional effect was accompanied by a slight (15%) but statistically insignificant increase in the binding of 3H-nitrendipine to striatal membranes from ethanol-treated rats as compared to control. The calcium-channel blocker, omega-conotoxin (500 nM) had no effect on voltage-dependent calcium uptake into synaptosomes prepared from control or ethanol-treated rats. Conotoxin (500 nM) inhibited the voltage-dependent release of endogenous dopamine from synaptosomes isolated from both groups by 36-44%. Ethanol (200 mM) added in vitro to control synaptosomes did not alter conotoxin's inhibition of dopamine release but completely abolished the omega-conotoxin-induced inhibition of dopamine release in synaptosomes isolated from ethanol-treated animals. These results suggest that DHP-sensitive and omega-conotoxin-sensitive calcium channels in rat brain respond differentially to chronic exposure to ethanol.
将两组成年Sprague-Dawley大鼠维持在营养完全的液体饮食中。在一组中，通常由糊精提供的37%的卡路里被乙醇替代。动物维持这种饮食八周。体外添加乙醇（200 mM）显著抑制了对照突触体的钙内流和多巴胺释放，但未改变从乙醇处理的大鼠分离的突触体的钙内流或多巴胺释放。二氢吡啶钙通道激动剂Bay K 8644（1 nM）显著增加了用15 mM KCl去极化的对照突触体的钙内流和多巴胺释放。Bay K 8644（1 nM）对从乙醇处理的动物分离的突触体的钙内流或多巴胺释放均无显著影响。这种功能效应的丧失伴随着与对照相比，乙醇处理的大鼠纹状体膜上3H-尼群地平结合略有增加（15%），但在统计学上无显著意义。钙通道阻滞剂ω-芋螺毒素（500 nM）对从对照或乙醇处理的大鼠制备的突触体中电压依赖性钙摄取没有影响。芋螺毒素（500 nM）抑制了两组分离的突触体内源性多巴胺的电压依赖性释放36 - 44%。体外添加乙醇（200 mM）到对照突触体中并未改变芋螺毒素对多巴胺释放的抑制作用，但完全消除了ω-芋螺毒素对从乙醇处理的动物分离的突触体中多巴胺释放的诱导抑制作用。这些结果表明，大鼠脑中对二氢吡啶敏感和对ω-芋螺毒素敏感的钙通道对长期暴露于乙醇的反应不同。
