Dodd P R, Lewohl J M
Clinical Research Laboratory, Royal Brisbane Hospital Research Foundation, Brisbane 4029, Australia.
Ann N Y Acad Sci. 1998 May;844(1):50-58. doi: 10.1111/j.1749-6632.1998.tb08221.x.
Human alcoholics have reduced neuronal counts in certain brain regions, such as superior frontal cortex (SFC), where the form and quantity of synaptic γ-aminobutyric acid type A (GABA) receptor sites are atypical. We measured the expression of GABA receptor isoform mRNA and protein, since GABA receptor pharmacology is strongly influenced by its subunit composition. Cortex samples were obtained at autopsy; whole-tissue extracts were assayed for mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), while synaptic membranes were studied for both GABA receptor pharmacology and subunit protein levels by Western blots with isoform-specific antibodies. Although α and α mRNA species were more strongly expressed in alcoholics irrespective of cirrhosis than in controls, α protein differed little between case groups, and α protein showed some complex variations. Differences in GABA pharmacology conformed more closely with differences in protein levels than with altered mRNA expression.
人类酗酒者某些脑区的神经元数量减少，如前额叶皮质（SFC），该区域γ-氨基丁酸A型（GABA）受体位点的形态和数量均不典型。由于GABA受体药理学受其亚基组成的强烈影响，我们检测了GABA受体亚型mRNA和蛋白质的表达。尸检时获取皮质样本；通过定量逆转录聚合酶链反应（RT-PCR）检测全组织提取物中的mRNA，同时用亚型特异性抗体通过蛋白质免疫印迹法研究突触膜的GABA受体药理学和亚基蛋白水平。尽管无论是否患有肝硬化，酗酒者的α和α mRNA种类表达均比对照组更强，但病例组之间的α蛋白差异不大，且α蛋白表现出一些复杂的变化。GABA药理学的差异与蛋白质水平的差异更密切相关，而非与mRNA表达改变相关。
