Chronic antidepressant treatment facilitates G protein activation of adenylyl cyclase without altering G protein content.
Chronic antidepressant treatment facilitates G protein activation of adenylyl cyclase without altering G protein content.
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发表时间：
1995-10
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通讯作者：
J. Chen;M. Rasenick
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作者：
J. Chen;M. Rasenick
有人认为抗抑郁作用的分子基础涉及受体后成分。我们的研究结果表明，G蛋白（Gs）是这些目标之一，慢性抗抑郁药治疗促进Gs α激活腺苷酸环化酶。本报告试图确定哪些方面的G蛋白功能改变慢性抗抑郁治疗。用阿米替林、地昔帕明、ABT 200（一种具有推定抗抑郁作用的吡咯烷）或电休克处理大鼠21天，并从大脑皮层制备膜。这些处理中的每一种都引起在鸟苷酰-5 '-亚氨基二磷酸（>或= 1 μ M）存在下测定的膜腺苷酸环化酶的增加。急性抗抑郁治疗的结果与对照治疗的结果没有差异。慢性治疗与安非他明，抑制神经递质再摄取，而不显示抗抑郁作用，也是无效的，在增加Gs α刺激腺苷酸环化酶。慢性抗抑郁治疗没有改变G蛋白的含量，因为通过免疫印迹检测到Gs α、Gi α、Go α或G β蛋白水平没有变化。虽然G蛋白的量没有变化，但抗抑郁药治疗增加了抗Gs α抗体免疫沉淀的活性Gs α/腺苷酸环化酶复合物的数量。有人建议，慢性抗抑郁药治疗改变某些膜组件，使更大比例的Gs α被激活，Gs α享有更富有成效的相互作用与腺苷酸环化酶，或两者兼而有之。
It has been suggested that the molecular basis of antidepressant action involves postreceptor components. Results from our studies have suggested that a G protein (Gs) is one of those targets and that chronic antidepressant treatment facilitates the activation of adenylyl cyclase by Gs alpha. This report represents an attempt to define which aspects of G protein function are altered by chronic antidepressant treatment. Rats were treated for 21 days with amitriptyline, desipramine, ABT 200 (a pyrollidine with putative antidepressant effects) or electroconvulsive shock, and membranes were prepared from the cerebral cortexes. Each of these treatments caused an increase in membrane adenylyl cyclase assayed in the presence of guanyl-5'-imidodiphosphate (> or = 1 microM). Results of acute antidepressant treatments were no different than those of control treatment. Chronic treatment with amphetamine, which inhibits neurotransmitter reuptake without displaying antidepressant effect, was also ineffective in increasing Gs alpha stimulation of adenylyl cyclase. Chronic antidepressant treatment did not change the content of G protein, as no change at the level of Gs alpha, Gi alpha, Go alpha or G beta protein was detected by immunoblotting. Although there was no change in the amount of G proteins, antidepressant treatment increased the number of active Gs alpha/adenylyl cyclase complexes immunoprecipitated by an anti-Gs alpha antibody. It is suggested that chronic antidepressant treatment alters certain membrane components such that a greater proportion of Gs alpha is activated, Gs alpha enjoys a more fruitful interaction with adenylyl cyclase, or both.