Maeztu A I, Ballesteros J, Callado L F, Gutiérrez M, Meana J J
Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia, Spain.
Alcohol Clin Exp Res. 1997 Nov;21(8):1479-83.
The status of the enzyme monoamine oxidase B (MAO-B) was directly evaluated in the postmortem brain from 20 alcoholics and 23 matched controls. The density of MAO-B sites was quantified by the specific binding of the selective inhibitor [3H]Ro 19-6327 (lazabemide) (8 nM) to cortical membranes. A positive correlation between age at death and MAO-B density was observed in the total sample (r = 0.37, p = 0.015). The density of MAO-B in alcoholics (Bmax = 1,263 +/- 131 fmol/mg of protein) was not different form that in control (Bmax = 1,131 +/- 96 fmol/mg of protein). Ethanol in vitro inhibited [3H]Ro 19-6327 binding, with similar potency in membranes form alcoholics (Ki = 280 +/- 13 mM) and controls (Ki = 338 +/- 84 mM). The present results in brain tissue contrast with previous reports of decreased MAO-B enzymatic activity in platelets of alcoholics, but strongly agree with recent genetic studies on MAO-B status in alcoholism.
对20名酗酒者和23名相匹配的对照者的死后大脑,直接评估了单胺氧化酶B(MAO-B)的状态。通过选择性抑制剂[3H]Ro 19-6327(拉扎贝胺)(8 nM)与皮质膜的特异性结合,对MAO-B位点的密度进行了定量。在整个样本中观察到死亡年龄与MAO-B密度之间呈正相关(r = 0.37,p = 0.015)。酗酒者中MAO-B的密度(Bmax = 1,263 +/- 131 fmol/mg蛋白质)与对照组(Bmax = 1,131 +/- 96 fmol/mg蛋白质)没有差异。体外乙醇抑制[3H]Ro 19-6327的结合,在酗酒者的膜(Ki = 280 +/- 13 mM)和对照组(Ki = 338 +/- 84 mM)中具有相似的效力。目前在脑组织中的结果与先前关于酗酒者血小板中MAO-B酶活性降低的报道形成对比,但与最近关于酗酒中MAO-B状态的遗传学研究结果高度一致。