Leslie S W, Barr E, Chandler J, Farrar R P
J Pharmacol Exp Ther. 1983 Jun;225(3):571-5.
Uptake of 45Ca++ by synaptosomes isolated from cerebral cortex, cerebellum, midbrain and brain stem of male, Sprague-Dawley rats was measured at 1-, 3-, 5-, 15-, 30- and 60-sec time periods. At 1 sec, the Ca++ uptake rate by cerebrocortical synaptosomes was 1.45 mumol/sec/g of protein, whereas the 60-sec rate was 0.03 mumol/sec/g of protein. In vitro addition of ethanol, 80 mM, inhibited depolarization-dependent (65 mM KCl) 45Ca++ uptake by synaptosomes but the time-response relationships varied depending upon the brain region studied. In cerebrocortical synaptosomes, ethanol significantly inhibited only the fast-phase component of 45Ca++ uptake (1 and 3 sec). Ethanol inhibited 45Ca++ uptake by midbrain synaptosomes at all measurement times studied (1, 3, 5 and 15 sec), whereas in cerebellum and brain stem ethanol inhibited 45Ca++ uptake at 3- and 5-sec time periods. Ethanol at concentrations of 25, 50, 100 and 150 mM inhibited 45Ca++ uptake by 9.0, 15.9, 24.8 and 30.7%, respectively, in cerebrocortical synaptosomes. In vitro ethanol, 80 mM, added to cerebrocortical synaptosomes isolated from rats fed a nutritionally adequate liquid ethanol diet did not significantly inhibit depolarization-dependent 45Ca++ uptake. The results of this study show that pharmacologically relevant ethanol concentrations inhibit voltage-dependent 45Ca++ uptake into synaptosomes. This inhibitory action may, at least in part, underlie some of the intoxicating effects of ethanol. In addition, chronic administration of ethanol resulted in an apparent adaptive response such that addition of ethanol no longer blocked 45Ca++ uptake. This adaptive response involving the calcium channel may represent a cellular mechanism for functional tolerance development.
在1秒、3秒、5秒、15秒、30秒和60秒的时间段内，测定了从雄性Sprague-Dawley大鼠的大脑皮层、小脑、中脑和脑干分离出的突触体对45Ca++的摄取情况。在1秒时，大脑皮层突触体对Ca++的摄取速率为1.45微摩尔/秒/克蛋白质，而60秒时的速率为0.03微摩尔/秒/克蛋白质。体外添加80 mM乙醇可抑制突触体对去极化依赖性（65 mM KCl）45Ca++的摄取，但时间-反应关系因所研究的脑区而异。在大脑皮层突触体中，乙醇仅显著抑制45Ca++摄取的快速相成分（1秒和3秒）。在所研究的所有测量时间（1秒、3秒、5秒和15秒），乙醇均抑制中脑突触体对45Ca++的摄取，而在小脑和脑干中，乙醇在3秒和5秒时间段抑制45Ca++摄取。在大脑皮层突触体中，浓度为25 mM、50 mM、100 mM和150 mM的乙醇分别抑制45Ca++摄取9.0%、15.9%、24.8%和30.7%。向从喂食营养充足的液体乙醇饮食的大鼠分离出的大脑皮层突触体中体外添加80 mM乙醇，并未显著抑制去极化依赖性45Ca++摄取。本研究结果表明，药理学相关浓度的乙醇可抑制突触体对电压依赖性45Ca++的摄取。这种抑制作用可能至少部分地是乙醇某些中毒作用的基础。此外，长期给予乙醇导致明显的适应性反应，使得添加乙醇不再阻断45Ca++摄取。这种涉及钙通道的适应性反应可能代表了功能耐受性发展的一种细胞机制。
