Kamada H, Ozawa H, Saito T, Hatta S, Takahata N
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Life Sci. 1997;60(1):57-66. doi: 10.1016/s0024-3205(96)00589-9.
We have investigated altered association of tubulin dimers interacting with G proteins and modulating adenylyl cyclase (AC) as a result of long-term amitriptyline (AMT) treatment. Gpp(NH)p-stimulated, but not basal or manganese-stimulated, AC activity was significantly augmented in cortex membranes prepared from rats chronically treated with AMT. The enhancement of AC activity by Gpp(NH)p-liganded tubulin (tubulin-Gpp(NH)p) was significantly higher in chronically AMT-treated rats than in control rats. Moreover, in cortex membranes from controls, tubulin-Gpp(NH)p prepared from chronically AMT-treated rats was more effective to activate AC activity than tubulin-Gpp(NH)p from controls. Immunoblotting and photoaffinity guanine nucleotide binding procedures showed no significant differences in the amount and the function of G proteins between controls and AMT-treated groups. It is suggested that long-term AMT treatment causes alteration in the functional interaction between tubulin and G protein, and this modification may participate in enhanced coupling of Gs to the catalytic subunit of AC induced by the chronic antidepressant treatment.
我们研究了长期使用阿米替林（AMT）治疗后，微管蛋白二聚体与G蛋白相互作用并调节腺苷酸环化酶（AC）的关联变化。在长期接受AMT治疗的大鼠制备的皮层膜中，Gpp(NH)p刺激而非基础或锰刺激的AC活性显著增强。与对照组大鼠相比，长期接受AMT治疗的大鼠中，Gpp(NH)p结合的微管蛋白（微管蛋白-Gpp(NH)p）对AC活性的增强作用显著更高。此外，在对照组的皮层膜中，由长期接受AMT治疗的大鼠制备的微管蛋白-Gpp(NH)p比对照组的微管蛋白-Gpp(NH)p更有效地激活AC活性。免疫印迹和光亲和鸟嘌呤核苷酸结合程序显示，对照组和AMT治疗组之间G蛋白的数量和功能没有显著差异。提示长期AMT治疗导致微管蛋白与G蛋白之间的功能相互作用发生改变，这种修饰可能参与了慢性抗抑郁治疗诱导的Gs与AC催化亚基增强的偶联。
