Yamaji T, Kagaya A, Okamoto Y, Hayashi T, Motohashi N, Yamawaki S
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Neuropsychobiology. 1996;33(2):55-9. doi: 10.1159/000119249.
The effects of antidepressants and calcium (Ca2+) antagonists on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Application of 5-HT (100 nM-100 microM) caused a rapid and reversible rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In the absence of extracellular Ca2+, the sustained phase of the [Ca2+]i response was strongly reduced, which was greater than the suppression of the initial peak. This suggests that the peak value is mainly due to internal Ca2+ storage sites, and the sustained phase is mainly composed of Ca2+ influx. The sustained phase was significantly attenuated by 100 nM clomipramine and verapamil. The present findings demonstrate that clomipramine and verapamil, in their therapeutic concentrations, have a common action of inhibiting Ca2+ influx, and suggest that the calcium antagonistic effect may play an important role in clinical effects of antidepressants.
采用数字成像显微镜技术,在单个C6BU-1胶质瘤细胞中研究了抗抑郁药和钙(Ca2+)拮抗剂对5-羟色胺(5-HT)诱导的Ca2+升高的影响。应用5-HT(100 nM - 100 microM)可引起细胞内Ca2+浓度([Ca2+]i)迅速且可逆地升高,呈浓度依赖性。在无细胞外Ca2+的情况下,[Ca2+]i反应的持续期显著降低,且降低程度大于初始峰值的抑制程度。这表明峰值主要归因于细胞内Ca2+储存位点,而持续期主要由Ca2+内流组成。100 nM氯米帕明和维拉帕米可显著减弱持续期。本研究结果表明,氯米帕明和维拉帕米在其治疗浓度下具有抑制Ca2+内流的共同作用,并提示钙拮抗作用可能在抗抑郁药的临床疗效中起重要作用。