A Study on Intracellular Calcium to Understand the Pathophysiology of Affective Disorders

我们研究了细胞内Ca^<2+>信号系统，以了解情感性障碍的病理生理。制备双相躁狂患者的血小板，测定细胞内Ca^<2+>。5- ht诱导躁狂症患者血小板细胞内Ca^<2+>动员显著高于对照组。此外，躁狂患者峰后的平台期也增强。我们研究了5-HT-2A受体介导的Ca^<2+>升高后的细胞内信号系统，我们发现5-HT-2A受体的激活促进了钙敏感的NO合成酶样活性，在胶质细胞中产生cGMP。锂是最常用的情绪稳定剂，被证明对中枢神经系统Ca^<2+>交换系统有效。锂抑制瓦苦因诱导的大鼠海马片细胞内Ca^<2+>升高。因此，锂似乎影响细胞内而不是细胞表面的受体。阿米替林、咪丙嗪、地西帕明和米安色林在高浓度下使原代培养的大鼠皮质神经元Ca^<2+>升高。抗抑郁药也使IP_3的形成增加到基础水平的150%。这些结果表明，抗抑郁药物直接激活细胞内信号通路，导致Ca^<2+>升高。此外，30mum丙咪嗪可降低去极化诱导的皮质神经元Ca^<2+>升高。丙咪嗪和阿米替林在10-50 muM浓度下抑制培养神经元细胞的自发振荡。三环类抗抑郁药是两亲性的，因此它们很容易穿透细胞膜，调节包括Ca^<2+>信号系统在内的大部分细胞内反应。GABA和NMDA增加了原代培养大鼠皮质神经元的Ca^<2+>，这些反应是由神经类固醇硫酸孕烯醇酮调节的。因此，研究细胞内Ca^<2+>信号系统对了解情感性障碍的病理生理具有重要意义。少

We have investigated intracellular Ca^<2+> signaling systems to understand the pathophysiology of affective disorders.1.Platelets form bipolar manic patients were prepared for intracellular Ca^<2+> measurement. 5-HT-induced intracellular Ca^<2+> mobilization in platelets from manic patients was significantly greater than that of control subjects. Moreover, plateau phase after the peak was also enhanced in manic patients.2.The intracellular signaling system following Ca^<2+> rise mediated by 5-HT-2A receptors was investigated, and we have found that an activation of 5-HT-2A receptors facilitates calcium-sensitive NO synthase-like activity, producing cGMP in the cells of glial origin.3.Lithium, which is the most popular mood stabilizer, is proved to be effective on Ca^<2+> exchanging system in the CNS.Lithium inhibited ouabain-induced intracellular Ca^<2+> rise in rat hippocampal slice. Thus, lithium appears to affect intracellular rather than receptors on the cell surface.4.Amitriptylin … More e, imipramine, desipramine and mianserin at high concentrations increased Ca^<2+> in primary cultured rat cortical neurons. The antidepressants also increased IP_3 formation up to 150 % of basal levels. These results indicate that antidepressant drugs directly activate intracellular signaling pathways, resulting in an increase in Ca^<2+>. Furthermore, 30 muM imipramine reduces depolarization-induced Ca^<2+> rise in cultured cortical neurons. Imipramine and amitriptyline, at the concentrations of 10-50 muM,inhibited spontaneous oscillations in cultured neuronal cells. Tricyclic antidepressants are amphiphilic so that they can easily penetrate cell membrane, regulating most of intracellular responses including Ca^<2+> signaling system.5.GABA,as well as NMDA,increased Ca^<2+> in primary cultured rat cortical neurons, and these response was modulated by pregnenolone sulfate, a neurosteoroid.Thus, it is important to investigate intracellular Ca^<2+> signaling system to understand the pathophysiology of affective disorders. Less