McGowan S, Eastwood S L, Mead A, Burnet P W, Smith C, Flanigan T P, Harrison P J
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Eur J Pharmacol. 1996 Jun 13;306(1-3):249-55. doi: 10.1016/0014-2999(96)00207-5.
GTP-binding proteins (G proteins) are heteromers composed of alpha, beta and gamma subunits. The expression of some G protein subunits is altered both by affective disorders and by antidepressant treatments. Here we have studied three G protein alpha subunit mRNAs in the hippocampus and frontoparietal cortex of rats treated with lithium for 14 days or with repeated electroconvulsive shock (five shocks over 10 days). After electroconvulsive shock, the three mRNAs changed differentially in the hippocampus. Specifically, Gs alpha mRNA was decreased in CA3 and CA1, whilst G(o) alpha mRNA was increased in dentate gyrus and Gi2 alpha mRNA was reduced in dentate gyrus and CA3. Lithium carbonate treatment produced a modest, uniform increase in the three mRNAs in dentate gyrus and CA3, and a selective elevation of G(o) alpha mRNA in CA1. Neither treatment altered the G protein mRNAs in the cortex nor cyclophilin mRNA in any region. These data extend the evidence that altered G protein expression is a part of the biochemical response to antidepressant treatments. Differences in the molecular and anatomical pattern of the alterations induced by electroconvulsive shock compared to lithium may contribute to their different therapeutic profiles.
GTP结合蛋白（G蛋白）是由α、β和γ亚基组成的异源三聚体。一些G蛋白亚基的表达会受到情感障碍和抗抑郁治疗的影响而发生改变。在此，我们研究了用锂治疗14天或反复电休克（10天内五次电击）的大鼠海马体和额顶叶皮质中的三种G蛋白α亚基mRNA。电休克后，海马体中的这三种mRNA发生了不同的变化。具体而言，CA3区和CA1区的Gsα mRNA减少，而齿状回中的G(o)α mRNA增加，齿状回和CA3区的Gi2α mRNA减少。碳酸锂治疗使齿状回和CA3区的这三种mRNA适度且均匀增加，CA1区的G(o)α mRNA选择性升高。两种治疗均未改变皮质中的G蛋白mRNA，也未改变任何区域的亲环蛋白mRNA。这些数据进一步证明，G蛋白表达改变是对抗抑郁治疗生化反应的一部分。与锂相比，电休克诱导的改变在分子和解剖模式上的差异可能导致它们不同的治疗效果。
