Eckert A, Gann H, Riemann D, Aldenhoff J, Müller W E
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Eur Arch Psychiatry Clin Neurosci. 1994;243(5):235-9. doi: 10.1007/BF02191580.
Many studies have demonstrated pharmacologic similarities between platelet and brain 5-HT2 binding sites. Therefore it may be possible to use platelets as a model for the central serotonergic neuron. Accordingly, a previous report (Kusumi et al. 1991b) about elevated [Ca2+]i after serotonin stimulation in platelets of depressed patients was interpreted as further evidence for enhanced serotonergic sensitivity in depression. However, a very recent study showed an enhanced thrombin-induced platelet Ca2+ response, rather suggesting abnormalities of intracellular Ca2+ regulation in affective disorders. In the present study we have determined 5-HT2- and thrombin-induced Ca2+ responses in platelets and additionally phytohemagglutin (PHA)-induced Ca2+ increase in lymphocytes of medicated depressed patients (8 mono- and 2 bipolar, HRSD > 17) and of ten sex- and age-matched controls. The results showed no significant difference in basal calcium levels between the two groups and no significant difference in the Ca2+ response to thrombin although the response was higher in the patients. The Ca2+ increase after serotonin stimulation in depressed patients was significantly (P < 0.05) higher than in healthy controls. By contrast, the Ca2+ response to PHA in lymphocytes was significantly decreased in the patients. Our data confirm elevated Ca2+ responses after 5-HT2 receptor activation even in mediated depressed patients. However, Ca2+ responses in lymphocytes were decreased. Together with the observations of an enhanced Ca2+ response in platelets after thrombin stimulation, we speculate that the findings rather suggest alterations of [Ca2+]i regulation in depression than specific changes of serotonergic sensitivity.
许多研究已证实血小板与脑5-羟色胺2（5-HT2）结合位点之间存在药理学相似性。因此，有可能将血小板用作中枢5-羟色胺能神经元的模型。相应地，之前一份关于抑郁症患者血小板经血清素刺激后细胞内钙离子浓度（[Ca2+]i）升高的报告（Kusumi等人，1991b）被解读为抑郁症中5-羟色胺能敏感性增强的进一步证据。然而，最近一项研究显示凝血酶诱导的血小板Ca2+反应增强，这反而提示情感障碍中细胞内Ca2+调节存在异常。在本研究中，我们测定了服药的抑郁症患者（8名单相抑郁和2名双相抑郁患者，汉密尔顿抑郁量表评分>17）以及10名年龄和性别匹配的对照者的血小板中5-HT2和凝血酶诱导的Ca2+反应，此外还测定了淋巴细胞中植物血凝素（PHA）诱导的Ca2+升高情况。结果显示，两组之间的基础钙水平无显著差异，凝血酶诱导的Ca2+反应也无显著差异，尽管患者的反应更高。抑郁症患者经血清素刺激后的Ca2+升高显著高于健康对照者（P<0.05）。相比之下，患者淋巴细胞对PHA的Ca2+反应显著降低。我们的数据证实，即使在服药的抑郁症患者中，5-HT2受体激活后Ca2+反应也会升高。然而，淋巴细胞中的Ca2+反应降低。结合凝血酶刺激后血小板中Ca2+反应增强的观察结果，我们推测这些发现提示抑郁症中[Ca2+]i调节存在改变，而非5-羟色胺能敏感性的特异性变化。
