Study on the function of monoamine receptors and transmembrane signal control in the affective disorders.

1)人血小板上存在的5 HT-2受体作为一种容易获得的外周模型，用于研究肾上腺素能神经元的某些功能，可能允许直接研究活体中5 HT-2受体的功能。在本研究中，我们评估了5 HT刺激的磷酸肌醇水解血小板从正常对照组和抑郁症患者治疗前。在一组年龄与正常对照组相匹配的未用药抑郁症患者中，我们发现5-HT（100 μ M）诱导的磷酸肌醇水解代谢产物1-磷酸肌醇（IP-1）的积累显著增加（抑郁症患者为基础值的150.7%，对照组为132.3%）。这一结果表明，5-HT刺激的磷酸肌醇代谢，由血小板中的5-HT-2受体介导，可能提供了一个有用的手段，研究抑郁症患者的肾上腺素能受体功能。2）我们研究了5-HT刺激的IP-1在大鼠脑片中的积累是否是由5-HT-2受体介导的，丙咪嗪及其组合对大脑皮层切片中的5 HT反应有任何影响。Ritanserin抑制5 HT刺激的IP-1积累，Ki值为20 nM。米安色林（1 μ M）、酮色林（1 μ M）和mCPP（100 μ M）可部分降低5 HT刺激的IP-1蓄积;螺哌隆（1 μ M）和普萘洛尔（1 μ M）未能阻断5 HT反应。这些结果表明，5-HT通过5-HT-2和5-HT-1c PI反应受体介导5-HT受体对磷脂酰肌醇的水解。用抑郁PCPA治疗10天导致IP-1的应答显著增加。

1) The presence of 5HT-2 receptors on the human platelets as a readily accessable peripheral model for certain functions of the serotonergic neuron, may permit direct study of the function of 5HT-2 receptors in living persons. In the present study, we have assessed 5HT-stimulated phosphoinositide hydrolysis in platelets from a normal control group and depressed subjects before treatment. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5HT(100uM)-induced accumulation of inositol-1-phosphate(IP-1), one metabolic product of phoshpoinositide hydrolysis(150 7% of basal for depressed patients, 132 3% for controls). This result suggested that 5HT-stimulated phosphoinositide metabolism, mediated by 5HT-2 receptors in platelets might be provide a useful mean of investigating serotonergic receptor function in depressed patients.2) We investigated whether 5HT-stimulated IP-1 accumulation in rat hippocampla slices is mediated by the 5HT-2 receptors, and a subchronic administration of PCPA, imipramine and in combination thereof has any effect on this 5HT response in the hippocampla slices. Ritanserin inhibit 5HT-stimulated IP-1 accumulation with a Ki value of 20nM. Mianserin(1uM), ketanserin(1uM) and mCPP(100uM) reduced partially 5HT-stimulated IP-1 accumulation; spiperone(1uM) and propranolol(1uM) failed to block the 5HT response. These results indicated that 5HT mediates its 5HT receptor on phosphoinositide hydrolysis through the 5HT-2 and 5HT-1c PI response receptors in the hippocampla slices. The 10-day treatment with Depression PCPA resulted in a significant increase in response of IP-1.