Armbrecht H J, Wood W G, Wise R W, Walsh J B, Thomas B N, Strong R
J Pharmacol Exp Ther. 1983 Aug;226(2):387-91.
In previous studies, we have shown that many of the pharmacological effects of ethanol administered in vivo are greater in older mice compared to younger mice. This study determined if there are age-related differences in membrane order when ethanol is administered in vitro. Synaptic plasma membranes, brain microsomal membranes and erythrocyte membranes were isolated from young (3-5 month), middle (11-13 months), and old (22-24 months) C57BL/6NNIA mice. The order parameter of each age group was measured using a 5-nitroxide stearic acid spin label in the presence of 0, 250 and 500 mM ethanol added in vitro. No age-related differences in order parameter were seen in the absence of ethanol. However, membranes from young animals were disordered to the greatest degree by ethanol. The synaptic plasma and erythrocyte membranes from young mice were disordered by both 250 and 500 mM ethanol. Membranes from old mice were disordered significantly by 500 mM ethanol only and the disordering was not as great as was seen in the membranes from the young mice. In the microsomal membrane preparation, 500 mM ethanol significantly disordered the membranes from the young animals, but it had no effect on membranes from old animals. Age differences were also observed generally for cholesterol and total phospholipid which both increased with increasing age for synaptic plasma and brain microsomes. Membrane disorder induced by ethanol differs with age and is associated with cholesterol and phospholipid content of membranes.
在先前的研究中,我们已经表明,与年轻小鼠相比,体内给予乙醇时,老年小鼠的许多药理作用更强。本研究确定了体外给予乙醇时,膜有序性是否存在与年龄相关的差异。从年轻(3 - 5个月)、中年(11 - 13个月)和老年(22 - 24个月)的C57BL/6NNIA小鼠中分离出突触质膜、脑微粒体膜和红细胞膜。在体外添加0、250和500 mM乙醇的情况下,使用5 - 硝基硬脂酸自旋标记物测量每个年龄组的有序参数。在没有乙醇的情况下,未观察到与年龄相关的有序参数差异。然而,乙醇对年轻动物的膜造成的无序程度最大。250和500 mM乙醇均使年轻小鼠的突触质膜和红细胞膜发生无序。仅500 mM乙醇使老年小鼠的膜显著无序,且无序程度不如年轻小鼠的膜。在微粒体制备中,500 mM乙醇使年轻动物的膜显著无序,但对老年动物的膜没有影响。突触质膜和脑微粒体中胆固醇和总磷脂通常也观察到年龄差异,二者均随年龄增长而增加。乙醇诱导的膜无序随年龄而异,且与膜的胆固醇和磷脂含量有关。