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

1)作为5-羟色胺能神经元某些功能的外周模型，5-羟色胺-2受体在人的血小板上的存在可以直接研究活人的5-羟色胺-2受体的功能。在这项研究中，我们评估了治疗前正常对照组和抑郁症受试者的5-羟色胺刺激的肌醇磷脂的血小板水解率。在一组年龄与正常对照组年龄匹配的未服药的抑郁症患者中，我们发现5-羟色胺(100uM)诱导的磷脂酰肌醇-1-磷酸(IP-1)的积聚显著增加(抑郁症患者为基础水平的150 7%，对照组为132 3%)。这一结果提示，5-羟色胺刺激的磷脂酰肌醇代谢可能是研究抑郁症患者5-羟色胺能受体功能的有用手段。2)我们研究了5-羟色胺刺激的大鼠海马片IP-1蓄积是否由5-羟色胺-2受体介导，亚慢性给药PCPA、丙咪嗪及其联合应用对5-羟色胺在海马片的这种反应有影响。Ritanserin抑制5HT刺激的IP-1积聚，Ki值为20 nm。米安色林(1uM)、酮色林(1uM)和mCPP(100uM)可部分抑制5HT刺激的IP-1积聚，螺环丙酮(1uM)和心得安(1uM)不能阻断5HT的作用。这些结果表明，5-羟色胺通过5-羟色胺-2和5-羟色胺-1c PI反应受体介导其5-羟色胺受体对磷脂酰肌醇的降解。用抑郁PCPA治疗10天后，IP-1的反应显著增加。

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.